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Biomedical subjects

J Malm

Publications and source records attributed to J Malm.

At least 37 records · Page 2Linked to original sources
PubMed2001

Outcome of laparoscopic splenectomy based on hematologic indication.

BACKGROUND: Laparoscopic splenectomy is the procedure of choice for elective splenectomy at the Cleveland Clinic Foundation. Although the literature clearly documents the technical feasibility and safety of laparoscopic splenectomy, little data exists concerning the results of this procedure based on the hematologic indication for splenectomy. We sought to examine the clinical experience with laparoscopic splenectomy in a single institution, with particular attention to morbidity and clinical outcomes based on hematologic disease process. METHODS: This study retrospectively reviewed a consecutive series of laparoscopic splenectomies performed for nontraumatic, splenic pathology at the Cleveland Clinic Foundation from August 1995 to January 2001. Patient demographics, operative indications, morbidity, mortality, and clinical outcome were evaluated. Hematologic diagnostic groups were compared using Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: A total of 147 laparoscopic splenectomies were performed. Seven patients (5%) required conversion to open splenectomy. Indications for splenectomy included idiopathic thrombocytopenic purpura (ITP) in 65 patients, hematologic malignancy in 43 patients, autoimmune hemolytic anemia (AIHA) in 9 patients, thrombotic thrombocytopenic purpura (TTP) in 9 patients, splenomegaly in 5 patients, splenic cyst in 4 patients, splenic abscess in 3 patients, hereditary spherocytosis in 2 patients, splenic artery aneurysm in 2 patients, Felty's syndrome in 1 patient, myelofibrosis in 1 patient, and other in 3 patients. Accessory spleens were identified in 20 patients (14%). Postoperative complications occurred in 23 (16%) patients. Patients with ITP had significantly shorter operation times (134 vs 163 min; p = 0.001), decreased estimated blood loss (126 vs 307 ml; p = 0.001), decreased length of hospital stay (2.8 vs 4.6 days; p < 0.001), and less chance of conversion (0 vs 7; p = 0.02) than patients with any other diagnosis. A mean follow-up period of 20 +/- 14 months showed an 85% rate of remission for ITP, 89% for TTP, and 89% for AIHA. Patients with malignant disease had significantly larger spleens (822 vs 313 g; p < 0.001), more estimated blood loss (380 vs 168 ml; p = 0.04), and longer operative times (170 vs 142 min; p = 0.009), as compared patients treated for benign disease. However, the length of hospital stay (4.3 vs 3.6 days; p = 0.06) and complication rates (19% vs 14%; p = 0.08) were not significantly different between the two groups. CONCLUSIONS: When performed for ITP, laparoscopic splenectomy resulted in shorter operations, minimal blood loss, earlier discharge, no conversions, and excellent remission rates, as compared with other hematologic indications. Despite larger spleens, more blood loss, and longer operations in patients with hematologic malignancies, morbidity and length of hospital stay still were similar to those associated with benign indications for laparoscopic splenectomy. In conclusion, laparoscopic splenectomy is safe and efficacious for a multitude of benign and malignant hematologic indications, and our data compares favorably to those for open series.

Adolescent↗
PubMed2001

Laparoscopic management and clinical outcome of emphysematous cholecystitis.

BACKGROUND: As opposed to acute, chronic, and acalculus cholecystitis, emphysematous cholecystitis (EC) is associated with significant morbidity and mortality. Only a few studies have specifically reviewed the operative management and clinical outcome of EC. This study documents the operative management and clinical outcome of EC at the Cleveland Clinic Foundation. METHODS: Between January 1996 and June 1999, 18 consecutive patients underwent cholecystectomy for emphysematous cholecystitis at our institution. All charts were reviewed retrospectively, and patients undergoing concurrent procedures were excluded. Mean values +/- standard deviation (SD) of the mean were calculated for patient demographics, preoperative white blood cell count (WBC), bilirubin, alkaline phosphatase, and length of hospital stay. Operative procedure (laparoscopic, converted, or open), preoperative imaging studies, operative time, ICU stay, morbidity, and mortality were reviewed. RESULTS: Patients presented with a mean age of 53.4 years (range, 18-80) and a male/female ratio of 3.5 (14/4). There were no differences between groups in terms of patient demographics. Mean WBC on admission was 14.2 K/mL (range, 5.4-19.7). Mean alkaline phosphatase and total bilirubin were 115 U/L (range, 45-428) and 1.4 mg/dl (range, 0.5-3.4), respectively. Thirteen patients (72%) were completed laparoscopically, two patients (11%) were converted to an open procedure, and three patients (17%) had open surgery. Overall mean length of hospital stay was 5 days (range, 1-18). Two patients from the open group ultimately died 1 year later due to progression of preexisting illness. One of these patients had congestive heart failure and chronic renal failure; the other had metastatic malignant melanoma. None of the patients died in the immediate perioperative period. There were five complications (27.8%). Two patients presented with bleeding secondary to heparin and coumadin therapy. One developed sepsis, and another developed leakage from the cystic duct stump, necessitating an endoscopic retrograde cholangiopancreatogram (ERCP) with stent decompression. The fifth complication, ileus, required readmission 3 days postoperatively, but the patient responded to conservative management. Complications were evenly distributed between the three groups. There were two complications in the laparoscopic group, two in the open group, and one in the conversion group. All other patients were alive at the time of this publication. CONCLUSIONS: Using current techniques, patients with EC can be managed successfully utilizing laparoscopy. Morbidity and mortality appear to be slightly higher than published reports for acute, chronic, and acalculus cholecystitis. Conversion rates are comparable to patients with acute and chronic cholecystitis who undergo laparoscopic cholecystectomy. Based on these data, laparoscopic cholecystectomy should be considered the first-line treatment for patients with known or suspected EC.

Adult↗
PubMed2001

Alpha-1-antitrypsin is present in the specific granules of human eosinophilic granulocytes.

Eosinophils may be found at sites of inflammation, for example in asthma, allergy and helminthic infestation, but their role in human inflammatory disease is unclear. In the present study, we investigated the presence of alpha-1-antitrypsin (AAT), a serine proteinase inhibitor, in human eosinophils. When lysates of highly purified eosinophils were subjected to Western blotting, with a chemiluminescent substrate, immunoreactive bands were seen. An ELISA was developed to measure the AAT content, which was found to be about 100 ng/5 x 106 eosinophils, about 50 ng/5 x 106 neutrophils, and about 25 ng/5 x 106 monocytes. Immunoelectron microscopy showed localization of AAT to the specific granules of eosinophils. During prolonged incubation of eosinophils, no significant increase in the total amount of AAT could be detected by ELISA. However, there was an increased level of AAT in the medium, in parallel with a decrease in the intracellular AAT content, suggesting release of preformed AAT. Apparent complex formation between iodinated elastase and AAT in eosinophil lysates provided evidence that the AAT is functionally active. On the basis of these findings it is suggested that by releasing AAT, eosinophils may, in a microenvironment, play a role in counteracting the tissue damage caused by serine proteinases released by neutrophils in inflammatory conditions.

Cytoplasmic Granules↗
PubMed2001

Bactericidal activity of human eosinophilic granulocytes against Escherichia coli.

Eosinophils participate in allergic inflammation and may have roles in the body's defense against helminthic infestation. Even under noninflammatory conditions, eosinophils are present in the mucosa of the large intestine, where large numbers of gram-negative bacteria reside. Therefore, roles for eosinophils in host defenses against bacterial invasion are possible. In a system for bacterial viable counts, the bactericidal activity of eosinophils and the contribution of different cellular antibacterial systems against Escherichia coli were investigated. Eosinophils showed a rapid and efficient killing of E. coli under aerobic conditions, whereas under anaerobic conditions bacterial killing decreased dramatically. In addition, diphenylene iodonium chloride (DPI), an inhibitor of the NADPH oxidase and thereby of superoxide production, also significantly inhibited bacterial killing. The inhibitor of nitric oxide (NO) production L-N(5)-(1-iminoethyl)-ornithine dihydrochloride did not affect the killing efficiency, suggesting that NO or derivatives thereof are of minor importance under the experimental conditions used. To investigate the involvement of superoxide and eosinophil peroxidase (EPO) in bacterial killing, EPO was blocked by azide. The rate of E. coli killing decreased significantly in the presence of azide, whereas addition of DPI did not further decrease the killing, suggesting that superoxide acts in conjunction with EPO. Bactericidal activity was seen in eosinophil extracts containing granule proteins, indicating that oxygen-independent killing may be of importance as well. The findings suggest that eosinophils can participate in host defense against gram-negative bacterial invasion and that oxygen-dependent killing, i.e., superoxide acting in conjunction with EPO, may be the most important bactericidal effector function of these cells.

Aerobiosis↗
PubMed2001

Two computerized methods used to analyze intracranial pressure B waves: comparison with traditional visual interpretation.

OBJECT: Slow and rhythmic oscillations in intracranial pressure (ICP), also known as B waves, have been claimed to be one of the best preoperative predictive factors in idiopathic adult hydrocephalus syndrome (IAHS). Definitions of B waves vary widely, and previously reported results must be treated with caution. The aims of the present study were to develop a definition of B waves, to develop a method to estimate the B-wave content in an ICP recording by using computer algorithms, and to validate these procedures by comparison with the traditional visual interpretation. METHODS: In eight patients with IAHS, ICP was continuously monitored for approximately 20 hours. The ICP B-wave activity as a percentage of total monitoring time (B%) was estimated by using visual estimation according to the definition given by Lundberg, and also by using two computer algorithms (Methods I and II). In Method I each individual wave was classified as a B wave or not, whereas Method II was used to estimate the B-wave content by evaluating the B-wave power in 10-minute blocks of ICP recordings. CONCLUSIONS: The two computerized algorithms produced similar results. However, with the amplitude set to 1 mm Hg, Method I yielded the highest correlation with the visual analysis (r = 0.74). At least 5 hours of monitoring time was needed for an acceptable approximation of the B% in an overnight ICP recording. The advantages of using modern technology in the analysis of B-wave content of ICP are obvious and these methods should be used in future studies.

Aged↗
PubMed2001

Cerebrospinal fluid hydrodynamics after placement of a shunt with an antisiphon device: a long-term study.

OBJECT: Few studies have been performed to investigate the cerebrospinal fluid (CSF) hydrodynamic profile in patients with idiopathic adult hydrocephalus syndrome (IAHS) before and after shunt implantation. The authors compared the in vivo CSF hydrodynamic properties, including the degree of gravity-induced CSF flow, of a shunt with an antisiphon device with a standard shunt. METHODS: Twelve patients with IAHS underwent insertion of shunts with Delta valves. Clinical testing, magnetic resonance imaging, and CSF hydrodynamic investigations were conducted with intracranial pressure (ICP), gravity effect, and pressure-flow curve of the shunt estimated at baseline and at 3 and 12 months postoperatively. No shunt was revised. Despite postoperative clinical improvement in all patients who received Delta valves, the mean ICP was only moderately reduced (mean decrease at 3 months 0.3 kPa [p = 0.02], at 12 months 0.2 kPa [not significant]). Patients with the greatest increase in ICP preoperatively had the most pronounced decrease postoperatively. The hydrostatic effect of the Delta valves was significantly lower than with the Hakim shunts (0.1-0.2 kPa compared with 0.6 kPa). The increased conductance (that is, lowered resistance) was up to 14 times higher with the Delta valves compared with preoperative levels. CONCLUSIONS: The function of a CSF shunt may be more complicated than previously thought; the subcutaneous pressure acting on the antisiphon device can modify the shunt characteristics. A compensatory increase in CSF production may counteract the increased outflow through the shunt. The improved CSF outflow conductance may increase the intracranial compliance and thereby dampen a pathological ICP waveform.

Aged↗
PubMed2001

Laparoscopic hernia repair enhances early return of physical work capacity.

Several researchers have documented less postoperative pain and a quicker return to daily activities after laparoscopic herniorrhaphy. However, little objective data that validates this hypothesis exists. This study compares the rate of postoperative physical work capacity with return to preoperative levels, which is measured by a standard treadmill test in patients who underwent laparoscopic and conventional open hernia repair. Patients completed a 6-minute walking test preoperatively and 1 week postoperatively using a nonmotorized treadmill. The distance walked was recorded. If the distance that a patient achieved at 1 week was not within 0.02 miles of the preoperative values of the patient, the patient was asked to return at 1 month for repeat testing. Patients were enrolled prospectively in this study from October 1997 to February 1999. Sixty-six patients participated in the study (27 laparoscopic herniorrhaphies and 39 open herniorrhaphies were performed). There was no significant difference in age, body mass index, or preoperative distance achieved among the two groups. At 1 week, patients who underwent laparoscopic repair demonstrated a mean increase of 18 meters from preoperative distance (P = 0.07). In the open group, patients demonstrated a mean decrease of 90 meters at 1 week (P = 0.001). The change in distance at 1 week between the laparoscopic and the open groups was statistically significant (P = 0.001). However, at 1 month, there was no significant difference among the two groups. Measured using treadmill walking, laparoscopic hernia repair seems to offer an early advantage to open repair in return-to-physical-work capacity.

Exercise Test↗
PubMed2000

Enzymatic action of prostate-specific antigen (PSA or hK3): substrate specificity and regulation by Zn(2+), a tight-binding inhibitor.

BACKGROUND: In semen, prostate-specific antigen (PSA or hK3) digests the gel proteins semenogelin I and II, resulting in liquefaction and the release of motile spermatozoa. We characterized the substrate specificity and zinc-mediated inhibition of PSA. METHODS: The proteolysis of human semenogelin I (SgI) and II (SgII) by PSA was characterized by purification of generated SgI and SgII fragments, N-terminal sequencing, and mass spectrometry. Zn(2+)-inhibition of PSA was studied using a chromogenic substrate. RESULTS: Eighteen cleavage sites in SgI and 16 in SgII were identified. Cleavages were identified mainly as the C-terminal of certain tyrosine and glutamine residues, but also the C-terminal of histidine, aspartic acid, leucine, serine, and asparagine residues. No cleavages were identified at any arginine, lysine, phenylalanine, tryptophan, or methionine residues, indicating that the substrate specificity of PSA is distinct from that of trypsin, chymotrypsin, tissue kallkrein (hK1), and kallikrein 2 (hK2). Zn(2+) ions have a dramatic effect on PSA activity; the data indicate that Zn(2+) is a tight-binding inhibitor of PSA activity. CONCLUSIONS: The data will enable the optimized design of PSA activity assays, which may prove instrumental to uncovering the role of PSA in cancer and reproduction. The inhibition data indicate that Zn(2+) could regulate PSA activity, which may prove important in the development of efficient inhibitors of PSA activity.

Amino Acid Sequence↗
PubMed2000

Three-year survival and functional outcome of patients with idiopathic adult hydrocephalus syndrome.

The functional outcome of 42 patients with idiopathic adult hydrocephalus syndrome (IAHS) was followed over a 3-year period after shunting. Survival curves were compared with those of age-matched healthy elderly subjects and patients with first-ever ischemic stroke. Twenty-seven patients with IAHS were improved 3 months after the operation and 11 remained improved at the 3-year follow-up. The case fatality in patients with stroke and those with IAHS was similar (32% versus 28%), but the relative risk of death among IAHS patients compared to a general elderly population was 3.3.

Aged↗
PubMed2000

The bactericidal/permeability-increasing protein (BPI) is membrane-associated in azurophil granules of human neutrophils, and relocation occurs upon cellular activation.

Neutrophilic granulocytes contain the 55 kDa bactericidal/permeability-increasing protein (BPI). BPI binds to lipopolysaccharides (LPS), and exerts bacteriostatic and bactericidal effects against a wide variety of Gram-negative bacterial species. We have investigated the subcellular location of BPI in immature and mature neutrophils using cryotechnique for immunoelectron microscopy. BPI was found to colocate with myeloperoxidase (MPO), a marker for azurophil granules, and it also showed the same pattern of distribution as CD63, a transmembrane-anchored protein. This suggests that BPI is membrane-associated in the azurophil granules in neutrophils. Its presence in azurophil granules was further confirmed by the finding of BPI in the azurophil granules of neutrophil promyelocytes of the bone marrow. Induction of selective release of azurophilic granules by the Na-ionophore monensin resulted in fusion of endosomes with azurophil granules, leading to the formation of large vacuoles containing MPO, CD63, and BPI. After phagocytosis of serum-treated zymosan (STZ), BPI was detected in phagosomes, both in association with membranes as well as in the lumen, suggesting the release of BPI into activated compartments. The results show that BPI is present in azurophil granules, is probably primarily membrane-associated, and is relocated after activation, following the same route as MPO and CD63.

Anti-Infective Agents↗
PubMed2000

Increased presence of cells containing transforming growth factor alpha (TGF-alpha) in ulcerative colitis, both during active inflammation and in remission.

OBJECTIVE: Patients with extensive and long-standing ulcerative colitis have an increased risk of developing colorectal cancer and sub-epithelial fibrosis. The polypeptide transforming growth factor alpha (TGF-alpha) has mitogenic effects and it is believed that local overproduction may result in tumour formation and fibrosis. DESIGN: In the present study, we correlated the presence of TGF-alpha in ulcerative colitis with the degree of inflammation and with dysplasia. METHODS: Sixty two patients were investigated, 46 with ulcerative colitis (16 with active inflammation and 20 in remission, 10 with dysplasia of the colon), and 16 controls with normal colonoscopy and without a history of colitis. There were no overlaps between the subgroups. Tissue sections from colonic biopsies were examined and TGF-alpha was detected by immunohistochemistry. TGF-alpha-containing cells were characterized by double-staining with antibodies to eosinophil cationic protein (ECP). An antibody (EG2) recognizing eosinophils with an activated phenotype was also used. RESULTS: The median number of TGF-alpha-containing cells in the mucosa was 24 per mm2 (inter-quartile range 10-51) in controls, 186 per mm2 (73-245) in ulcerative colitis with active inflammation, 76 per mm2 (52-198) in remission, and 130 per mm2 (66-203) in areas of dysplasia. Double-staining for TGF-alpha and ECP revealed that most of the TGF-alpha-containing cells were eosinophils, and most had an activated phenotype as judged by staining with EG2. CONCLUSIONS: The presence of TGF-alpha-containing cells in colonic mucosa is increased both in active inflammation and during remission in ulcerative colitis. Dysplasia is not associated with any significant increase in TGF-alpha-containing cells. The majority of TGF-alpha-containing cells are eosinophils with an activated phenotype. TGF-alpha released from these cells could be important for the development of complications seen in ulcerative colitis, such as cancer and fibrosis.

Adult↗
PubMed2000

The human cationic antimicrobial protein (hCAP-18) is expressed in the epithelium of human epididymis, is present in seminal plasma at high concentrations, and is attached to spermatozoa.

Innate immunity is important for the integrity of the host against potentially invasive pathogenic microorganisms in the environment. Antibiotic peptides with broad antimicrobial activity are part of the innate immune system. We investigated the presence of the cathelicidin, human cationic antimicrobial protein (hCAP-18), in the male reproductive system. We found strong expression of the hCAP-18 gene by in situ hybridization and hCAP-18 protein, as detected by immunohistochemistry, in the epithelium of the epididymis, but not in the testis. The highest expression in the epididymis was in the caudal part. Western blotting showed a doublet band, the upper part corresponding to the size of hCAP-18 in plasma and neutrophils. Using a specific enzyme-linked immunosorbent assay (ELISA), levels of 86.5 +/- 37.8 microg/ml (mean +/- standard deviation; range, 41.8 to 142.8 microg/ml; n = 10) were detected in seminal plasma from healthy donors, which is 70-fold higher than the level in blood plasma. Flow cytometry and immunocytochemistry revealed the presence of hCAP-18 on spermatozoa. ELISA measurement showed levels of 196 ng/10(6) spermatozoa, corresponding to 6.6 x 10(6) molecules of hCAP-18 per spermatozoon. Our results suggest a key role for hCAP-18 in the antibacterial integrity of the male reproductive system. The attachment of hCAP-18 to spermatozoa may implicate a role for hCAP-18 in conception.

Anti-Bacterial Agents↗
PubMed1999

Hyperhomocysteinemia and hypofibrinolysis in young adults with ischemic stroke.

BACKGROUND AND PURPOSE: Data from epidemiological and case-control studies suggest that increased total homocysteine (tHcy) levels are associated with increased risk for thromboembolic disease. The mechanisms by which hyperhomocysteinemia contributes to thrombogenesis are incompletely understood. The main objectives of this study of young ischemic stroke patients were (1) to examine fasting and post-methionine load levels of tHcy, (2) to ascertain the genotype frequency of the C677CT mutation in the methylenetetrahydrofolate reductase gene (TT genotype), and (3) to study the possible interaction between plasma tHcy levels and fibrinolytic factors. METHODS: This case-control study was based on 80 consecutive patients aged 18 to 44 years admitted between January 1992 and May 1996 as a result of a first-ever ischemic stroke. Forty-one healthy control subjects were recruited. Measurement of fasting tHcy and post-methionine load levels and evaluation of the fibrinolytic system were undertaken at least 3 months (mean, 5.1+/-1. 9 months) after admission. Genotyping of the methylenetetrahydrofolate reductase gene was performed. RESULTS: Although the increase after methionine loading (ie, postload tHcy minus fasting-level tHcy) was significantly higher among patients, there was no difference in fasting and postload tHcy levels. After adjustment for conventional risk factors, elevated postload increase tHcy levels were associated with a 4.8-fold increased risk of ischemic stroke. There was no difference between patients and control subjects in either TT genotype frequency or T allele frequency. Abnormal response to methionine loading was associated with higher tissue plasminogen activator (tPA) mass concentration, higher plasminogen activator inhibitor-1 levels, and lower tPA activity. After adjustment for age, sex, body mass index, serum cholesterol, and triglycerides, an abnormal increase in postload tHcy levels remained significantly associated with tPA mass concentration levels (P=0.03). CONCLUSIONS: A moderately elevated increase in tHcy levels after methionine loading was associated with an increased risk for ischemic stroke in young adults. In contrast, fasting tHcy levels did not differ between patients and controls. A moderately elevated increase in tHcy after methionine loading may provide a additional thrombogenic risk mediated in part by interactions with the fibrinolytic system. In young stroke patients, a methionine loading test to detect hyperhomocysteinemia should always be considered in the convalescent phase of the disease.

Adolescent↗
PubMed1998

[Hemicraniectomy in malignant mid-cerebral infarction. Further trials needed before its acceptance in clinical practice].

In cases of completed middle cerebral artery territory stroke, prognosis is very poor and the clinical course is characterised by a rapid decline in consciousness and signs of herniation 2-4 days after the onset of symptoms due to a space-occupying mass. Failure of conservative therapy is the rule, and herniation is the usual cause of death, occurring in almost 80 per cent of cases. Recently published results have suggested that hemicraniectomy may improve survival in patients with massive hemisphericstroke, decreasing mortality to less than 35 per cent. The article presents what is probably the first case to be reported in Sweden, where hemicraniectomy was performed on a 45-year-old woman with right hemispheric completed middle cerebral artery infarction.

Cerebral Infarction↗
PubMed1998

Semenogelin I and semenogelin II, the major gel-forming proteins in human semen, are substrates for transglutaminase.

The major seminal vesicle secreted proteins in human semen, semenogelin I and semenogelin II, interact non-covalently and via disulphide bridges to instantly form a coagulum upon ejaculation. The coagulum is liquefied after a few minutes due to the action of a prostatic serine protease, prostate-specific antigen (PSA). In contrast to rat semen, which forms an insoluble plug within minutes of expulsion, no transglutaminase-mediated cross-linking has been demonstrated in ejaculated human semen. However, we here show that semenogelin I and semenogelin II, both in seminal vesicle fluid and purified from semen, are substrates for factor XIIIa, the fibrin cross-linking transglutaminase. The cross-linking of the semenogelins, which was conformation-dependent, and the incorporation of a fluorescence-labelled amine, were visualised by SDS/PAGE and Western blot. Purified semenogelin I and semenogelin II could be cross-linked separately into complexes. Moreover, digestion of semenogelin with PSA produced fragments, some of which were cross-linked into complexes by factor XIIIa. We also found that PSA was unable to release any semenogelin fragments during exposure of the high molecular-mass complexes of cross-linked semenogelin to active PSA.

Cadaverine↗
PubMed1998

Eosinophil leukocyte degranulation in response to serum-opsonized beads: C5a and platelet-activating factor enhance ECP release, with roles for protein kinases A and C.

BACKGROUND: Eosinophils have a typical content of granule-bound, cytotoxic, cationic proteins which may, when released to the external milieu, play roles in diseases such as asthma and parasitic infestation. Therefore, we have investigated possible mechanisms by which their release is regulated in eosinophils. METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to detect released eosinophil cationic protein (ECP). Release of ECP was induced by serum-opsonized, nonphagocytosable Sephadex beads (SOS). RESULTS: The complement fragment C5a and platelet-activating factor (PAF) were found to enhance ECP release in response to SOS in a dose-dependent fashion, and, contrary to previous reports, they were not found to act as secretagogues themselves on eosinophils in suspension. The role of protein kinase C (PKC) in eosinophil degranulation has been controversial. We found that ECP release induced by SOS was inhibited by the PKC inhibitors staurosporine and calphostin C. Activation of protein kinase A (PKA), by raising cAMP, also inhibited ECP release. Furthermore, pertussis toxin decreased ECP release on opsonized beads, indicating the involvement of pertussis-toxin-sensitive G proteins. CONCLUSIONS: C5a, and PAF enhance granule release, rather than acting as secretagogues themselves. PKC and PKA have opposing roles in the regulation of ECP release in response to SOS.

Blood Proteins↗
PubMed1998

Effects of transient and persistent cerebrospinal fluid drainage on sleep disordered breathing in patients with idiopathic adult hydrocephalus syndrome.

OBJECTIVES: To examine sleep disordered breathing including obstructive sleep apnoea in patients with idiopathic adult hydrocephalus syndrome (IAHS) and to study the effects of CSF drainage and shunting procedure on sleep disordered breathing. METHODS: In 17 patients with IAHS polysomnographic investigations were performed before and after lumbar CSF drainage and after shunt operation. RESULTS: Baseline investigations documented a high prevalence of sleep related obstructive respiratory events (respiratory disturbance index >10 in 65% of the patients) and impaired sleep structure. There was no correlation between respiratory disturbance index and CSF pressure. Minimum oxygen saturation was highly correlated with cognitive function. Neither lumbar CSF drainage nor shunting alleviated the respiratory disturbance index. REM and delta sleep increased initially after shunting but there was no sustained effect on sleep quality. CONCLUSIONS: Sleep disordered breathing is a prevalent finding in patients with IAHS. The shortcoming of CSF drainage to improve sleep disordered breathing either transiently or permanently implies that sleep disordered breathing is a coexistent condition, or an irreversible consequence of the hydrocephalus, with a potential of causing additional dysfunction in IAHS.

Aged↗