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Dexamethasone suppresses the generation of phenylhydrazine-induced anemia in the rat.

The immunoactive steroid dexamethasone (DXM) was administered to rats injected with a dose of phenylhydrazine (PHZ) known to induce anemia. PHZ treatment alone resulted in a hemolytic anemia that was most pronounced on Days 1-7 after injection. This anemia was accompanied by a leukocytosis that was greatest on Days 2-7 following PHZ treatment. Lymphocytes accounted for greater than 75% of this incremental increase. In contrast, rats treated with PHZ as well as with DXM displayed erythrocyte counts and hematocrits within the normal range. Although the reticulocyte counts of these rats were higher than those of controls, they were significantly lower than those of animals receiving PHZ alone. In addition, DXM suppressed the leukocytosis and splenomegaly resulting from PHZ administration and inhibited the rise in plasma IgG titers induced by PHZ exposure. DXM also altered the ratio of peripheral blood T and B lymphocytes of PHZ-treated rats. DXM suppression of PHZ-induced anemia is further confirmation that this anemia is associated with immune activation.

Anemia, Hemolytic↗

Nonocclusive mesenteric ischemia in a patient on maintenance hemodialysis.

UNLABELLED: Nonocclusive mesenteric ischemia (NOMI) is known to occupy about 25% to 60% of intestinal infarction. NOMI has been reported to be responsible for 9% of the deaths in the dialysis population and the postulated causes of NOMI include intradialytic hypotension, atherosclerosis and medications, such as diuretics, digitalis and vasopressors. Clinical manifestations, such as fever, diarrhea and leukocytosis, are nonspecific, which makes early diagnosis of NOMI very difficult. CASE: A 66-year-old woman on maintenance hemodialysis for 5 years was admitted with syncope, abdominal pain and chilly sensation. Since 7 days prior to admission, blood pressure on the supine position during hemodialysis had frequently fallen to 80/50 mmHg. Four days later, she complained of progressive abdominal pain. Rebound tenderness and leukocytosis (WBC 13900/mm3) with left shift were noted. Stool examination was positive for occult blood. Abdominal CT scan showed a distended gall bladder with sludge. Under the impression of acalculous cholecystitis, she was operated on. Surgical and pathologic findings of colon colon were compatible with NOMI. Because of recurrent intradialytic hypotension, we started midodrine 2.5 mg just before hemodialysis and increased the dose up to 7.5 mg. After midodrine therapy, blood pressure during dialysis became stable and the symptoms associated with hypotension did not recur. CONCLUSION: As NOMI may occur within several hours or days after an intradialytic hypotensive episode, abdominal pain should be carefully observed and NOMI should be considered as a differential diagnosis. In addition, we suggest that midodrine be considered to prevent intradialytic hypotensive episodes.

Aged↗

Unsuspected bacterial infections in febrile convulsions.

In a 12-month prospective study in 1984, blood and urinary cultures were obtained as a routine from 307 children who presented with fever and convulsions to the Mater Misericordiae Children's Hospital, Brisbane, and the results were compared with data from 1981-1983 when cultures were not taken as a routine. In the prospective study, bacteraemia was found in 12 (4.3%) of 282 patients but was not suspected clinically in half of these; urinary-tract infection was found in seven (2.6%) of 272 patients and in six of these it was not suspected clinically. All 12 patients with unsuspected bacteraemia or urinary-tract infection had persistent fever; of these, nine patients suffered simple convulsions and all cases of urinary-tract infection occurred in female patients. Bacteraemia was significantly more common in patients of less than two years of age, in children who were selected for lumbar puncture and in the study period compared with the retrospective period, 1981-1983. Leukocytosis (white-cell count, more than 15.0 X 10(9)/L) was a sensitive (75%) diagnostic aid but was poorly specific (59%) for bacteraemia. Bacterial meningitis was not diagnosed initially in four of the nine cases which occurred among children who presented with fever and convulsions between 1981 and 1984; in all four children, the cerebrospinal fluid appeared normal at hospital admission. We conclude that bacteraemia and urinary-tract infections are detected more frequently in children who are admitted to hospital with febrile convulsions when cultures are performed as a routine. In the at-risk group (children of less than two years of age), the prevalence of urinary-tract infection is increased in female patients and the prevalence of bacteraemia is increased in those patients who are selected for lumbar puncture. The use of leukocytosis as a criterion to determine the need for blood cultures improves the diagnostic yield but would result in increased costs and additional venepuncture. Bacterial meningitis was rare in our case series and the performance of a lumbar puncture as a routine at admission to hospital would not have led to its earlier diagnosis.

Acute Disease↗

[Bladder carcinoma producing granulocyte colony stimulating factor (G-CSF). A case report].

A 69-year-old woman was admitted to the hospital complaining of general fatigue and lower abdominal pain. She had undergone total cystectomy because of invasive recurrent bladder carcinoma three months ago. Histopathological diagnosis was transitional cell carcinoma (TCC) grade 3 and squamous cell carcinoma (SCC), pT3a. A goose egg-sized painful mass was noticed at the lower abdominal region. A CT scan revealed an intrapelvic fist-sized mass and suggested tumor recurrence with ileus caused by intestinal invasion. The laboratory examination showed remarkable leukocytosis of 79,700/mm3 in the peripheral blood and serum analysis revealed high value of granulocyte colony stimulating factor (G-CSF), 240 pg/ml (normal: less than 30 pg/ml). In spite of active treatment, the patient died of cachexia about a month after detection of the leukocytosis. The autopsy showed that the recurrent tumor had positive immunohistochemical staining for G-CSF, and the bone marrow had reactive proliferation mainly by granulocytes. From these findings, this case was diagnosed as bladder carcinoma producting G-CSF. G-CSF producting tumor of the bladder is very rare. This was the 8th case in Japanese literatures. The previous reports were reviewed and discussed.

Aged↗

West Nile virus in raptors from Virginia during 2003: clinical, diagnostic, and epidemiologic findings.

Sixty-one birds of prey admitted to The Wildlife Center of Virginia (WCV; Waynesboro, Virginia, USA) from June to November 2003 were tested for West Nile virus (WNV) infection. Choanal and/or cloacal swabs were obtained and submitted to Virginia's Division of Consolidated Laboratory Services (Richmond, Virginia, USA) for analysis with real-time reverse transcriptase polymerase chain reaction (RT-PCR). Forty birds of prey were positive for WNV by RT-PCR. Five avian families and nine species of raptors were represented, with great horned owls (Bubo virginianus) and red-tailed hawks (Buteo jamaicensis) most frequently affected. Presenting clinical signs were consistent with previous reports of WNV infection in raptors; however, these differed between species. Of WNV positive birds, nonspecific signs of illness were the most common clinical findings, particularly in red-tailed hawks; signs included dehydration (n = 20), emaciation (n = 18), and depression (n = 15). Neurologic abnormalities were frequently identified, especially in great horned owls, and included head tremors (n = 17), ataxia (n = 13), head incoordination (n = 7), torticollis (n = 3), nystagmus (n = 3), and head tilt (n = 3). Great horned owls exhibited anemia and leukocytosis with heterophilia, eosinophilia, and monocytosis consistent with chronic inflammation. Red-tailed hawks were anemic with a heterophilic leukocytosis and regenerative left shift. The majority of WNV cases occurred during August and September; there was a marked increase in the number of raptors admitted to WCV during these months followed by a marked decrease during October, November, and December. This pattern differed from mean monthly admissions during the previous 10 years and suggests a negative impact on local raptor populations. The effects of WNV on avian populations are largely unknown; however, because of their ecological importance, further investigation of the effects of WNV on raptor populations is warranted.

Animals↗

Causes of erroneous white blood cell counts and differentials in clinically healthy young northern elephant seals (Mirounga angustirostris).

From 1993 to 1995, approximately 10% of the clinically healthy northern elephant seals (Mirounga angustirostris) at The Marine Mammal Center in California exhibited a large unexplained increase in their white blood cell (WBC) count. In these animals, WBC counts ranged from 28,780 to 125,000/mm3, with a mean of 50,087/mm3. Significant correlations between the leukocytosis and weight gain and day of admittance were identified, but no correlation existed between leukocytosis and general state of health, sex, length of stay, or diet. Bone marrow contamination of blood samples, erroneous automated leukocyte counts, and leukogram changes consistent with subclinical inflammation were the major factors contributing to the elevated WBC counts in these apparently clinically healthy animals.

Animals↗

Laparoscopic versus open treatment of patients with acute cholecystitis.

BACKGROUND/AIMS: The studies published so far mention a high rate of complication and conversion in laparoscopic surgical treatment of acute cholecystitis. Considering the relatively high conversion rate in cases of acute cholecystitis, it is necessary to pre-operatively estimate the chance of successful laparoscopic cholecystectomy. One of the aims of this study was to determine the factors that influence the chance of success of this technique. Another aim was to define possible advantages of the method. METHODOLOGY: From 1991 through to 1995, a total of 295 patients in whom acute cholecystitis had been diagnosed on the basis of clinical examination, laboratory data, ultrasonography and pathohistological examination, underwent operative therapy. The laparoscopic approach was attempted in 49 of these patients. Since the patients who underwent primary open surgery were markedly handicapped with regard to severity of inflammation and co-morbid factors, we identified a sub-group of these patients who were comparable to those who underwent laparoscopic cholecystectomy in accordance of the above-mentioned criteria. RESULTS: The rate of conversion (44.9%) correlated with the severity of inflammation, which was determined on the basis of leukocytosis > 10 x 10(9)/l (p = 0.004) and the pathohistological diagnosis (p = 0.005). Hence, the rate of conversion was 71.4% in cases of empyema of the gallbladder but only 29.2% in cases of edematous cholecystitis. In patients whose leukocyte count decreased within 4 days of conservative treatment, a successful laparoscopic cholecystectomy (LC) was performed in 91.7% (11/12) of cases, while 8 patients whose leukocyte count increased or showed no reduction during this time required conversion to open cholecystectomy (p = 0.0001). In cases of acute cholecystitis, the complication rate after LC is lesser in respect of wound infection (p = 0.07) and pneumonia (p = 0.04). In all patients, obesity was a risk factor for wound infection (p = 0.04). Injury to the small intestine was registered in 1 case but in no case was LC associated with injury to the bile duct. CONCLUSIONS: The degree of inflammation and its response to conservative treatment, which are determined on the basis of leukocytosis and clinical improvement, are clear indications of the chance of successful delayed laparoscopic cholecystectomy within the first week. Hence, all patients whose leukocyte count does not decrease after antibiotic treatment should be treated with open cholecystectomy (OC). The complication rate following LC is less than that following OC. Although no injury to the bile duct has been observed in cases of acute cholecystitis, major complications are possible and should not be excluded.

Acute Disease↗

[Adult-onset Still's disease. Report of 5 cases].

The authors report 5 cases of Still's disease in adults whose symptoms were mainly characterised by high fever, transient exanthema, polyarthralgia and/or polyarthritis, lymphoadenomegaly, splenomegaly and neutrophil leukocytosis. Assays for leukocytosis were positive, as were those for inflammatory markers and serum ferritin was also high in all 3 patients in which it assayed. On the contrary, serum ferritin latex test, Waaler-Rose reaction and all other tests commonly used to diagnose long-term fevers were all negative. All the subjects examined recovered after prolonged steroid therapy. Only one patient reported severe sequelae in the hip joints and subsequently underwent bilateral hip replacement surgery.

Female↗

Gangrenous cholecystitis: analysis of risk factors and experience with laparoscopic cholecystectomy.

BACKGROUND: Gangrenous cholecystitis occurs in up to 30% of patients admitted with acute cholecystitis. Factors predicting gangrenous disease in patients with acute cholecystitis remain poorly defined, making preoperative diagnosis difficult. Identification of these factors and early diagnosis of gangrenous cholecystitis will indicate more aggressive treatment, earlier operation, and a lower threshold for conversion of laparoscopic to open cholecystectomy. METHODS: We reviewed our experience with acute cholecystitis during the 2-year period of 1995 to 1996. Admitting history, physical examination, operative report, laboratory and radiology data, and pathology report were analyzed for each patient. Acute cholecystitis and its gangrenous complication were diagnosed by both gross and microscopic examination. RESULTS: One hundred fifty-four patients were admitted to the hospital with acute cholecystitis and underwent cholecystectomy; gallbladder gangrene was found in 27 (18%) of these patients. Four patients with gallbladder gangrene underwent open cholecystectomy and 23 patients underwent laparoscopic cholecystectomy, of which 15 (65%) were completed laparoscopically and 8 (35%) had open conversion as a result of severe inflammation. Risk factors for gallbladder gangrene included male gender, age older than 50 years, history of cardiovascular disease, and leukocytosis greater than 17,000 white blood cells/mL. CONCLUSIONS: Older male patients (age older than 50 years) with history of cardiovascular disease, leukocytosis greater than 17,000 white blood cells/mL, and acute cholecystitis have increased risk of gallbladder gangrene and conversion of laparoscopic cholecystectomy to open cholecystectomy. Urgent laparoscopic cholecystectomy with low threshold for conversion to open cholecystectomy should be considered in these patients at high risk for gallbladder gangrene.

Acute Disease↗

[T-cell prolymphocytic leukemia with CD4+8+25+ phenotype in a patient presenting with venous thrombosis in the lower leg].

A 58-year-old man was referred to our hospital because of painful swelling in the left lower leg and leukocytosis in January 1999. Moderate hepatosplenomegaly but no lymph node swelling was observed. Marked leukocytosis (leukocytes 44.9 x 10(4)/microliter with 95% morphologically prolymphocytes) and thrombocytopenia were detected. The surface phenotype of the leukemia cells was CD1-2+3+5+7+4+8+25+. Magnetic resonance imaging revealed dilated veins in the left lower leg. An abnormal 47XY, +22 karyotype was detected in 1/20 cells. Tests for HTLV-I antibody were negative. A diagnosis of T-cell prolymphocytic leukemia (T-PLL) was made on the basis of data including cytochemical and electron microscopic findings. Although 2 courses of chemotherapy comprising vincristine, cyclophosphamide, and prednisolone improved the venous thrombosis in the leg, the leukemia cells were refractory to chemotherapy. To prevent the recurrence of venous thrombosis due to leukostasis, the patient underwent repeated leukapheresis. The leukocyte count was maintained at around 20.0 x 10(4)/microliter after total 7 courses of leukapheresis, one course of which comprised 7l of extracorporeal circulation. In addition to the rare presentation of venous thrombosis, the CD4+8+25+ phenotype observed in this case is rare in patients with T-PLL.

CD4-CD8 Ratio↗

[RS3PE syndrome or benign edematous polysynovitis in the elderly. Study of 8 cases].

BACKGROUND: The RS3PE syndrome is a recently described uncommon disorder in the elderly patient; in the initial reports, it was characterized by an excellent prognosis with total remission. In contrast with rheumatoid arthritis and polymyalgia rheumatic, it has been related to HLA B7. Further works have questioned its benign nature and even that it is a new entity. Our objective was to study the clinico-biological characteristics, therapy, and clinical course in patients with RS3PE attended at our clinic. METHODS: Retrospective descriptional study of patients with RS3PE attended in our clinic from January 1992 to December 1998 following the inclusion criteria proposed by Olivé et al. For all patients, the following determinations and studies were performed: complete blood count, ESR, serum biochemistry, two measurements of rheumatoid factor (RF), and X-ray. Class I HLA typing was determined in five cases. RESULTS: Eight patients were found (6 men and 2 women), with a mean age of 68.7 years. The arthritis was more common at MCP, wrists, shoulder, and PIF in hands. Four patients had tenosynovitis of the hand flexors. ESR (mean: 69.3) and RCP (mean: 49.7) were increased in most cases. Seven patients had leukocytosis. HLA B7 was positive for 4 out of five patients. All patients were treated with low-dose corticosteroids, with a mean length of 9.5 months. Three patients had relapses. During follow-up after therapy had been completed, none of the patients had other diseases. CONCLUSIONS: RS3PE syndrome involves elderly patients and its clinical course is characterized by sudden onset seronegative symmetrical polysynovitis, with pitting edema over the hand dorsum and less commonly over the pretibial region. In most cases, a marked acute-phase reaction and leukocytosis were observed. Therapy with low-dose corticosteroids is effective; sometimes however, it is necessary to add antimalarial agents. The three patients who relapsed had underlying diseases: chronic lymphocytic leukemia, Sjögren's syndrome, and liver cirrhosis, respectively. The diagnosis of RS3PE should be obtained a posteriori, after a prolonged follow-up of the patient. Atypical cases, with evolution towards other rheumatic or hematological disorders or as paraneoplastic manifestation, have been reported.

Age Factors↗

Some biological and immunological properties of extracellular slime from Pseudomonas aeruginosa.

Extracellular slime from 8 different Pseudomonas aeruginosa strains was extracted and purified. All slime-preparations exhibited immunogenic properties in rabbits vaccinated with detoxified or not detoxified slime. The antisera of both groups of immunized animals possessed strong hemagglutination activity against homologous slime. Immune hemagglutinins were present in the IgM and IgG fractions of serum globulins. The high value of these antibodies was found in rabbit's sera short after injection of slime-extract. The hemagglutinins quickly reached the peak value and maintained in serum over 60-70 days. Biological properties of lyophilized slime-preparations were defined in rabbit-skin test, local Shwartzman test, pyrogenic reaction and measured as LD50 for mouse. Intravenous injection of slime elicited marked changes in the number of leukocytes in the peripheral blood of rabbit. The animals responded to slime either with leukopenia passing into leukocytosis or with leukocytosis without leukopenia.

Animals↗

[A case of emphysematous pyelonephritis improved with conservative therapy--indication for conservative therapy].

A 51-year-old female patient was hospitalized in our department with high fever and left flank pain. Laboratory examination showed leukocytosis, increase of C-reactive protein (CRP), hyperglycemia and renal insufficiency. Enterobacter aerogenes grew out of the cultured urine. The radiograph and computerized tomographic (CT) scan revealed streaky gas in the destroyed left renal parenchyma with perirenal gas. She was diagnosed with left emphysematous pyelonephritis. Antibiotics therapy, treatment for sepsis and disseminated intravesicular coagulation was initiated resulting in mitigation of inflammation. High blood glucose initially required insulin therapy, but finally returned to normal levels through administration of oral antidiabetics. Although leukocytosis and low grade fever continued, the patient was discharged on day 53 with a negative CRP. CT scan indicated that the emphysematous change was localized after three months and almost resolved after four months. Renal scintigram indicated the residual function of the affected kidney. Because of the possibility of residual renal function and the cure by conservative therapy alone, the conservative therapy is preferred when the initial treatment is effective.

Anti-Bacterial Agents↗

[Epidemiologic-clinical aspects of tick borne borreliosis in the Szczecin Province].

The aim of the study was to assess if Szczecin voivodeship is an area of endemic borreliosis, assess the risk due to B. burgdorferi infection in habitants and evaluate clinical manifestations of borreliosis. The study was conducted in 1993-1995, material comprised 299 persons (211 men and 88 women) aged from 3 to 78 years, divided into two groups. Group I consisted of foresters working in four forestry districts, occupationally exposed to tick bite. Group II was completed of Szczecin voivodeship habitants, sporadically exposed to tick bite. Control group consisted of 30 healthy persons without exposure to tick bite. Research programme of study comprised epidemiologic data, clinical examination, evaluation of serum anti-B.b antibodies in all persons and assessment of some infectious parameters (red cells sedimentation--RCS, leukocytosis and C-Reactive Protein--CRP) during borreliosis. High prevalence of borreliosis was noted in both groups. Risk of borreliosis was similar in four forestry districts (Tab. 1). The hazard of infection was not restricted to forest areas only but was present in some parts of Szczecin and its suburbs (parks and gardens). Infection by B.b. was observed in both males and females in all age groups. Risk of B.b infection increased accordingly to duration of exposure but in some examined persons after single tick bite the disease developed (Tab. 2). Some of infected persons do not demonstrate clinical symptoms of borreliosis (Tab. 3). In most cases the disease was diagnosed in early stage of infection (Tab. 4). During infection different organs and systems were involved (Tab. 5). In clinical study skin was the most often affected organ followed by nervous system and joints (Tab. 5, 7). Clinical manifestations comprised erythema migrans chronicum, radiculitis, arthritis, meningitis, encephalitis and uveitis (Tab. 6). Serological study revealed the presence of serum anti-B.b antibodies in 47.6% of examined persons with occupational risk involving tick bite, and 32.7% persons of sporadic risk with negative serology of borreliosis in control group (Tab. 8). The parameters of acute inflammatory phase (RCS, CRP, leukocytosis) are of limited value in diagnosis of borreliosis.

Adolescent↗

Multi-cellular activation in vivo by endotoxin in humans--limited protection by adenosine infusion.

The influence of adenosine infusion (40 microg/kg/min for 4 h) on inflammatory and hemostatic parameters was investigated in healthy males without (n = 10) or with (n = 11) intravenous endotoxin injection (4 ng/kg). Without endotoxin, adenosine elevated circulating leukocytes and circulating platelet-leukocyte aggregates. Endotoxin activated platelets and leukocytes in vivo. Platelet activation was seen as slightly increased platelet P-selectin expression, decreased platelet counts, and elevated plasma soluble P-selectin (from 39.6 +/- 3.4 to 68.9 +/- 6.6 ng/ml, P<0.01). Leukocyte activation was evidenced by increased CD1 lb expression (from MFI of 0.54 +/- 0.02 to 2.21 +/- 0.17; P<0.01) and plasma elastase levels (from 25.3 +/- 2.5 to 169.3 +/- 22.5 ng/ml: P <0.01). Endotoxin also enhanced platelet and leukocyte responsiveness to in vitro stimulation. Endotoxin induced von Willebrand factor secretion (from 92 +/- 8 units to 265 +/- 19 units at 4 h; P <0.001) and enhanced thrombin generation in vivo. Endotoxin induced leukocytosis and thus increased circulating platelet-leukocyte, mainly platelet-neutrophil, aggregates. Adenosine caused slight attenuation of platelet reactivity to agonist stimulation, enhanced the endotoxin-induced leukocytosis, and detained more platelet-leukocyte aggregates in circulation, but did not attenuate endotoxin-induced neutrophil elastase secretion, von Willebrand factor secretion, or thrombin generation. Thus, endotoxemia induces multi-cellular activation in vivo. Adenosine inhibits leukocyte adhesion and extravasation, and mildly attenuates platelet responsiveness and soluble P-selectin release. Adenosine has the potential of becoming a therapeutic antiinflammatory drug, but an optimal treatment strategy needs to be developed.

Adenosine↗

Hematology of the neonatal calf. II. Response associated with acute enteric infections, gram-negative septicemia, and experimental endotoxemia.

The hematological responses of neonatal calves with acute enteric infections were compared to the responses of calves with septicemia and experimentally induced endotoxemia. The mean hematocrit of septicemic calves (45.0% +/- 7.8) was similar to that of calves with primary enteric infections (45.3% +/- 7.0) but the total plasma protein concentration of septicemic calves (5.8g/100 ml +/- 0.69) was significantly lower than that of calves with primary enteric infections (8.6 g/100 ml +/- 1.5). The difference in total plasma protein concentration was due primarily to the hypogammaglobulinemia observed in septicemic calves. The leukocytic response to septicemic calves was similar to that of nonsepticemic calves with enteric infections. In most calves of both groups, moderate but significant leukocytosis and neutrophilia were observed. Marked leukopenia was observed terminally in 2 of 9 septicemic calves but in only 1 of 26 calves with primary enteric infections. Leukopenia was a characteristic finding in calves with experimental endotoxemia. Leukopenia developed within 5 minutes following intravenous administration of endotoxin and persisted until death in most calves. In calves which lived 12 hours or longer, there was a biphasic leukocytic response with leukocytosis being observed 24 hours following endotoxin administration.

Animals↗

Leukocyte mobilization induced by hypervolemia is due to a combined alpha- and beta-adrenoceptor activation.

A phenomenon of leukocytosis induced by hypervolemic stress was discovered. Although a single injection of 350 microl of saline (equivalent to approx. 70 ml in humans, 1 ml/kg of body weight) did not have an effect on the leukocyte counts in long-term intravenously cannulated, freely behaving rats, a single injection of 750 microl of saline (equivalent to approx. 150 ml in humans, 2.1 ml/kg) induced rapid leukocytosis of 160% within 1 minute followed by a gradual increase up to 180% after 1 hour. Measurement of serum norepinephrine concentration revealed a significant increase in rats of the hypervolemic group, compared with those of the low volume group. Pretreatment with either the beta-adrenoceptor antagonist nadolol or the selective alpha2-adrenoceptor antagonist yohimbine prevented both leukocyte peaks in the high volume group, suggesting a combined receptor activation. This critical dependence of leukocyte counts on changes in blood volume should be taken into consideration in experiments with laboratory animals (the quantity of volume applications can falsify results of experiments).

Adrenergic alpha-Antagonists↗

Specific and rapid scintigraphic detection of infection with 99mTc-labeled interleukin-8.

UNLABELLED: Interleukin-8 (IL-8) is a chemotactic cytokine involved in activation and recruitment of neutrophils to areas of infection. In our previous studies in rabbits we tested 123I-labeled IL-8 for its potential to image infections and showed that IL-8 rapidly and efficiently accumulated in infectious foci. However, labeling of IL-8 with 123I is costly and laborious and the specific activity of the preparation was low. In this study IL-8 was labeled with 99mTc through the hydrazinonicotinamide (HYNIC) chelator. METHODS: The leukocyte receptor-binding capacity of the preparation was determined in vitro. Rabbits with Escherichia coli abscesses were injected intravenously with 7 MBq 99mTc-HYNIC-IL-8. Biodistribution of the radiolabel was determined by gamma camera imaging and tissue counting at 8 h after injection. 99mTc-HYNIC-lysozyme was used as a size-matched control. RESULTS: The leukocyte receptor-binding capacity of the 99mTc-HYNIC-IL-8 preparation was preserved as determined in vitro, but labeling efficiency was modest with a specific activity of 3 MBq/microg. 99mTc-HYNIC-IL-8 accumulated rapidly in the abscess up to 0.33 +/- 0.06 percentage injected dose per gram (%ID/g) at 8 h after injection (vs. 0.025 +/- 0.003 %lD/g for 99mTc-HYNIC-lysozyme). Total uptake in the abscess was 4.9 +/- 0.7 %ID (vs. 0.44 +/- 0.05 %ID for 99mTc-HYNIC-lysozyme). Abscess-to-contralateral muscle ratios increased up to 127 +/- 23 (compared with 6.7 +/- 1.1 for 99mTc-HYNIC-lysozyme) and abscess-to-blood ratios increased to 11.9 +/- 2.2 (0.24 +/- 0.03 for 99mTc-HYNIC-lysozyme). The radiolabel was excreted renally, with a retention in the kidneys of 28 %ID. Gamma camera imaging rapidly visualized the abscess from 1 h after injection onward, with abscess-to-background ratios improving with time up to 22 at 8 h after injection (vs. 2.7 for 99mTc-HYNIC-lysozyme), as determined by quantitative analysis of the images. Most important, only a transient (30 min) moderate drop of leukocyte counts and no leukocytosis were observed after injection of an imaging dose of 99mTc-HYNIC-IL-8. CONCLUSION: IL-8 can be labeled with 99mTc using HYNIC as a chelator. By this method the leukocyte receptor-binding capacity is preserved. The preparation allows rapid visualization of infection in a rabbit model with high target-to-background ratios. The mild transient drop of leukocyte counts and the absence of leukocytosis suggest that 99mTc-HYNIC-IL-8 may be used as an imaging agent with only mild and transient side effects.

Abscess↗