Biomedical subjects

S Appel

Publications and source records attributed to S Appel.

At least 19 recordsLinked to original sources

PubMed2006

Role of dendritic cells in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic inflammatory and lymphoproliferative autoimmune disease of unknown aetiology. It is characterised by progressive mononuclear cell infiltration of the salivary and lacrimal glands and a decreased glandular secretion, resulting in dryness of the mouth and eyes (xerostomia and keratoconjunctivitis sicca, respectively). Dendritic cells (DC) are considered to be the most potent antigen-presenting cells. Because of their central role in initiating an immune response while maintaining tolerance, impaired function of these cells might lead to the break of peripheral tolerance and initiation of immune responses to self-antigens. This review will focus on the possible role of DC in SS.

Animals↗

PubMed2005

Factors influencing susceptibility to compulsive dopaminergic drug use in Parkinson disease.

BACKGROUND: In the course of treatment, a small group of patients with Parkinson disease (PD) develop a harmful pattern of compulsive dopaminergic drug use, called the dopamine dysregulation syndrome (DDS). Individual factors may influence susceptibility. OBJECTIVES: To identify predisposing factors to DDS in a population of outpatients with PD. METHODS: The authors compared clinical features, impulsive sensation seeking (ISS) personality traits, past experimental drug use, alcohol consumption, smoking behaviors, and depressive symptoms in 25 patients with DDS to an outpatient sample of 100 patients with PD who were not compulsively overusing dopaminergic medication. RESULTS: Patients with DDS had a significantly younger age at disease onset, higher dopaminergic drug intake, greater past experimental drug use, more depressive symptoms, scored higher on ISS ratings, and tended to have higher alcohol intake. Using logistic regression analysis, we found that novelty seeking personality traits, depressive symptoms, alcohol intake, and age at PD onset were significant predictors of DDS. CONCLUSIONS: These factors may help to identify early patients who are more vulnerable to developing a pattern of compulsive dopaminergic drug use and help minimize its consequences.

Adult↗

PubMed2001

Perceptions about complementary therapies relative to conventional therapies among adults who use both: results from a national survey.

BACKGROUND: Little is known about perceptions of complementary and alternative medical (CAM) therapy relative to conventional therapy among patients who use both. OBJECTIVE: To document perceptions about CAM therapies among persons who use CAM and conventional therapies. DESIGN: Nationally representative, random-household telephone survey. SETTING: The 48 contiguous U.S. states. PARTICIPANTS: 831 adults who saw a medical doctor and used CAM therapies in 1997. MEASUREMENTS: Perceptions about helpfulness and patterns of CAM therapy use relative to conventional therapy use and reasons for nondisclosure of CAM therapies. RESULTS: Of 831 respondents who saw a medical doctor and used CAM therapies in the previous 12 months, 79% perceived the combination to be superior to either one alone. Of 411 respondents who reported seeing both a medical doctor and a CAM provider, 70% typically saw a medical doctor before or concurrent with their visits to a CAM provider; 15% typically saw a CAM provider before seeing a medical doctor. Perceived confidence in CAM providers was not substantially different from confidence in medical doctors. Among the 831 respondents who in the past year had used a CAM therapy and seen a medical doctor, 63% to 72% did not disclose at least one type of CAM therapy to the medical doctor. Among 507 respondents who reported their reasons for nondisclosure of use of 726 alternative therapies, common reasons for nondisclosure were "It wasn't important for the doctor to know" (61%), "The doctor never asked" (60%), "It was none of the doctor's business" (31%), and "The doctor would not understand" (20%). Fewer respondents (14%) thought their doctor would disapprove of or discourage CAM use, and 2% thought their doctor might not continue as their provider. Respondents judged CAM therapies to be more helpful than conventional care for the treatment of headache and neck and back conditions but considered conventional care to be more helpful than CAM therapy for treatment of hypertension. CONCLUSIONS: National survey data do not support the view that use of CAM therapy in the United States primarily reflects dissatisfaction with conventional care. Adults who use both appear to value both and tend to be less concerned about their medical doctor's disapproval than about their doctor's inability to understand or incorporate CAM therapy use within the context of their medical management.

Adult↗

PubMed2001

Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum.

To determine the role of immune/inflammatory factors in dopaminergic cell degeneration in parkinsonian substantia nigra, we assayed tyrosine hydroxylase (TH)-positive immunoreactive neuronal numbers with stereologic techniques and CD11b-positive immunoreactive microglial profiles following 6-hydroxydopamine (6-OHDA) injection into ipsilateral striatum of mice. We further investigated the effect of minocycline on the inhibition of microglial activation and subsequent protection of nigral cells. The relative number of microglial profiles in the substantia nigra (SN) ipsilateral to the injection increased from 31 to 32% 1-3 days after injection, and increased further to 55% by 7 days and 59% by 14 days, compared with the contralateral SN. These changes started prior to the decrease of TH immunoreactivity of 34% on day 7 and of 42% by day 14. In animals treated with minocycline, microglial activation was inhibited by 47%, and TH positive cells were protected by 21% at day 14 after 6-OHDA injection, compared with those parkinsonian animals without minocycline treatment. All these results suggest that microglial activation may be involved in the nigral cell degeneration in 6-OHDA induced parkinsonian mice.

Animals↗

PubMed2001

Optimization of differential photodynamic effectiveness between normal and tumor urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as sensitizer.

Photodynamic therapy using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX is a promising tool in bladder-cancer therapy. However, little is known about the cellular mechanisms of phototoxicity. Our aim was to characterize the cellular damage and to optimize differential photodynamic effectiveness between tumor and normal urothelial cells. RT4 tumor and UROtsa normal urothelial cells were used to simulate a papillary bladder tumor in contrast to normal urothelium. Photodynamically induced damage in plasma membrane and mitochondria was monitored by flow cytometry with propidium iodide exclusion and analysis of aggregate formation of the dye JC-1. Cell morphology was investigated by phase-contrast and fluorescence microscopy following acridine orange staining. Long incubation times (3 hr) led to complete RT4 tumor cell kill accompanied by a marked fraction of damaged normal UROtsa cells. Shorter incubation intervals (1 hr) also resulted in complete RT4 tumor cell kill; however, most UROtsa cells retained their cell properties, including intact plasma membrane and active mitochondria as well as intact cellular morphology. Phototoxicity depends not only on cellular sensitizer accumulation but also on intracellular localization. Analysis of phototoxic mechanisms is an important step for planning combination therapy regimens with, e.g., DNA-damaging agents. Further, data indicate that differential phototoxicity in normal and tumorous urothelium can be enhanced using differences in cellular protoporphyrin IX distribution following short 5-ALA incubation times. These data are encouraging for the in vivo situation since short incubation times are a more practical approach for local photodynamic therapy of early tumor stages not only in the bladder but also, e.g., in the gastro-intestinal tract or bronchial mucosa.

Aminolevulinic Acid↗

PubMed2001

Identification and localization of a new human myotubularin-related protein gene, mtmr8, on 8p22-p23.

Myotubularin and myotubularin-related proteins are dual-specificity phosphatases. Several myotubularin-related proteins have been identified in humans and mice. The members of the myotubularin protein family are highly conserved, from humans to yeast. Mutations in the human myotubularin gene (MTM1) lead to X-linked myotubular myopathy. Here we isolate and localize a novel putative myotubularin-related protein gene (MTMR8) on chromosome 8p22--p23,between the markers D8S550 and D8S265, by exon-trapping experiments and RT-PCR. Genomic sequencing revealed that the gene consists of 10 exons and spans approximately 43 kb. The corresponding cDNA is 7081 bp. The open reading frame predicts a protein of 549 amino acids and a calculated molecular mass of 63 kDa. Like myotubularin-related protein-5, MTMR8 has no dual-specificity phosphatase domain. It contains a double-helical motif similar to the SET interaction domain, which is thought to have a role in the control of cell proliferation.

Amino Acid Sequence↗

PubMed1999

Vocal fold nodules in adult singers: regional opinions about etiologic factors, career impact, and treatment. A survey of otolaryngologists, speech pathologists, and teachers of singing.

This study was undertaken to better understand current regional opinions regarding vocal fold nodules in adult singers. A questionnaire was sent to 298 persons representing the 3 professional groups most involved with the care of singers with vocal nodules: otolaryngologists, speech pathologists, and teachers of singing. The questionnaire queried respondents about their level of experience with this problem, and their beliefs about causative factors, career impact, and optimum treatment. Responses within and between groups were similar, with differences between groups primarily in the magnitude of positive or negative responses, rather than in the polarity of the responses. Prevailing opinions included: recognition of causative factors in both singing and speaking voice practices, optimism about responsiveness to appropriate treatment, enthusiasm for coordinated voice therapy and voice training as first-line treatment, and acceptance of microsurgical management as appropriate treatment if behavioral management fails.

Adult↗

PubMed1998

Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey.

CONTEXT: A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990. OBJECTIVE: To document trends in alternative medicine use in the United States between 1990 and 1997. DESIGN: Nationally representative random household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997, respectively. PARTICIPANTS: A total of 1539 adults in 1991 and 2055 in 1997. MAIN OUTCOMES MEASURES: Prevalence, estimated costs, and disclosure of alternative therapies to physicians. RESULTS: Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8% in 1990 to 42.1% in 1997 (P < or = .001). The therapies increasing the most included herbal medicine, massage, megavitamins, self-help groups, folk remedies, energy healing, and homeopathy. The probability of users visiting an alternative medicine practitioner increased from 36.3% to 46.3% (P = .002). In both surveys alternative therapies were used most frequently for chronic conditions, including back problems, anxiety, depression, and headaches. There was no significant change in disclosure rates between the 2 survey years; 39.8% of alternative therapies were disclosed to physicians in 1990 vs 38.5% in 1997. The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 (64.0%) and 1997 (58.3%) (P=.36). Extrapolations to the US population suggest a 47.3% increase in total visits to alternative medicine practitioners, from 427 million in 1990 to 629 million in 1997, thereby exceeding total visits to all US primary care physicians. An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and/or high-dose vitamins (18.4% of all prescription users). Estimated expenditures for alternative medicine professional services increased 45.2% between 1990 and 1997 and were conservatively estimated at $21.2 billion in 1997, with at least $12.2 billion paid out-of-pocket. This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations. Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $27.0 billion, which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services. CONCLUSIONS: Alternative medicine use and expenditures increased substantially between 1990 and 1997, attributable primarily to an increase in the proportion of the population seeking alternative therapies, rather than increased visits per patient.

Adult↗

PubMed1998

Protein modification by the lipid peroxidation product 4-hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients.

We report increased modification of proteins by 4-hydroxynonenal (HNE), a product of membrane lipid peroxidation, in the lumbar spinal cord of sporadic amyotrophic lateral sclerosis (ALS) patients versus that of neurologically normal controls. By immunohistochemistry, HNE-protein modification was detected in ventral horn motor neurons, and immunoprecipitation analysis revealed that one of the proteins modified by HNE was the astrocytic glutamate transporter EAAT2. Given that the function of proteins modified by HNE can be severely compromised as previously demonstrated for glutamate transporters in cortical synaptosome preparations, our findings suggest a scenario in which oxidative stress leads to the production of HNE, impairment of glutamate transport, and excitotoxic motor neuron degeneration in ALS.

Aged↗

PubMed1998

Prevalence of and factors associated with current and lifetime depression in older adult primary care patients.

BACKGROUND: Depression in late life is a significant health problem in the United States. This study examined the relationship between depression and alcohol, cigarette use, family history, and sociodemographic factors in older adult primary care patients. METHODS: As part of a larger clinical trial, 2,732 patients in 24 primary care offices were recruited to complete a self-administered health screening survey. Depression was assessed using Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) criteria for lifetime and current depression. RESULTS: A total of 17.8% of females and 9.4% of males age 60 and over met DSM-III-R criteria for lifetime depression; 10.6% of the females and 5.7% of the males met current depression criteria. Depression was significantly and positively correlated with female gender and family history of mental health problems and negatively correlated with social contact. CONCLUSIONS: Older adults, especially women, should be considered at elevated risk for depression when a family history of mental health problems and self-report of inadequate social connection can be established.

Aged↗

PubMed1997

First pharmacokinetic-pharmacodynamic study in humans with a selective 5-hydroxytryptamine4 receptor agonist.

This report describes the first study in humans with SDZ HTF 919 (HTF), a novel, selective 5-hydroxytryptamine4 (5-HT4) receptor partial agonist and investigates its tolerability, pharmacokinetics, and pharmacodynamics. Three cohorts of 12 men, of whom 8 were treated with active drug and 4 with placebo, participated in the double-blind, randomized, parallel-group, ascending-dose study. A single dose and subsequently twice-daily multiple doses of 25, 50, and 100 mg were given for 14 days. Adverse events, clinical laboratory variables, electrocardiogram, vital signs, and psychometric effects were recorded. Basic pharmacokinetic characteristics of HTF were derived. Loose stool and total colonic transit time were assessed. Mild to moderate adverse gastrointestinal events, predominantly loose stools, occurred at all dose levels and reflect the pharmacologic properties of HTF. The incidence of headache increased with dose. Dose-normalized (to 25 mg) systemic exposures were 25 +/- 12, 19 +/- 11, and 26 +/- 10 hr.ng/mL in single doses and 26 +/- 12, 23 +/- 12, and 33 +/- 12 hr.ng/mL in multiple doses for the three doses. Steady-state concentrations of HTF were reached after 8 days of daily administration and moderate accumulation was observed. Loose stool occurred on average between 2 and 4 hours after drug administration. The overall HTF-mediated median decrease from baseline (26 and 38 hours) in total colonic transit time was 4.8 hours, versus 1.8 hours with placebo. In conclusion, the novel 5-HT4 receptor agonist HTF was tolerated at oral doses of 25 mg to 100 mg administered twice daily. Pharmacokinetics in both single and multiple doses indicate no deviation from dose proportionality. The applicability of the total colonic transit time as a measurement of surrogate prokinetic effect warrants further investigation in patient populations.

Adult↗

PubMed1997

Clinical pharmacodynamics of SDZ HTF 919, a new 5-HT4 receptor agonist, in a model of slow colonic transit.

OBJECTIVES: To explore the pharmacodynamic effects of the new promotile agent SDZ HTF 919, a selective partial 5-HT4 receptor agonist, in healthy subjects. METHODS: A pharmacodynamic model was applied to prolong colonic transit by dietary means. Subsequently, the effects of twice-daily multiple doses of SDZ HTF 919 (1, 5, 25, and 100 mg) were investigated in a randomized, double-blind, placebo-controlled parallel-group study with 12 subjects per dose level. The sequential design with three study periods of 7 days each included intake of a self-selected diet, a liquid formula diet with soluble fiber supplementation, and a fiber-supplemented diet together with either SDZ HTF 919 or placebo administration. Stool characteristics (frequency and consistency) and total colonic transit times (with use of radiopaque markers) were recorded in each study period. RESULTS: SDZ HTF 919 was well tolerated at all dose levels. The frequency of loose stool and headache increased with higher doses. After a fiber-supplemented diet intake, the median stool frequency decreased from 8 1/2-9 to 5-7 defecations per study period. SDZ HTF 919 in doses of 25 and 100 mg twice a day increased the stool frequency (p < 0.05). Stool consistency was softened by all but the lowest SDZ HTF 919 dose. A fiber-supplemented diet prolonged total colonic transit time in all groups by 45 hours on average. Twice-a-day administration of SDZ HTF 919 for 6 days in addition to a fiber-supplemented diet significantly shortened the total colonic transit time only at the 5 mg dose. The lack of effect at lower and higher SDZ HTF 919 doses suggests a biphasic dose-response relationship for total colonic transit time. CONCLUSIONS: The suitability of total colonic transit time measurements in healthy subjects as a surrogate marker should be confirmed by patient studies.

Adult↗

PubMed1996

Assessment and rehabilitation of children with special needs.

Evaluating the visual functioning of children with multiple impairments has long been a source of frustration for many eye care practitioners. A reflection of this difficulty is seen in the number of persons with multiple handicaps, especially children who are labeled "untestable" or "blind" by eye care specialists, but whose parents, teachers, and other caregivers know have some residual vision. These children with special needs may not be responsive to standard testing procedures for a variety of reasons. Stress-related behaviors, orthopedic and neuromuscular disorders, mental retardation, and preverbal levels of development will often greatly interfere with communication and co-operation levels. As parents, educators, and rehabilitation professionals have become aware of the importance of vision in the development of any child, the demand for comprehensive functional vision evaluations has substantially increased. The purpose of this paper is to present a functional vision evaluation for a child with special needs. Although one case is given as an example, guidelines for the evaluation of all special needs children are presented. It is important for eye care specialists to utilize these examination procedures in order to provide a framework from which comprehensive vision services can be delivered in conjunction with available community resources.

Child↗

PubMed1996

Pupillary dilation and funduscopy with 1.0% hydroxyamphetamine plus 0.25% tropicamide (Paremyd) versus tropicamide (0.5 or 1.0%) as a function of iris and skin pigmentation, and age.

BACKGROUND: This study was designed to evaluate the effect of Paremyd, a combination of 1.0 percent hydroxyamphetamine hydrobromide and 0.25 percent tropicamide, on pupil size during binocular indirect ophthalmoscopy (BIO) upon 164 subjects of various skin pigmentation, iris color, and age. METHODS: Pupillary dilation and ease of performing BIO were measured after 30 minutes following instillation of a single drop of either Paremyd or tropicamide (1.0 or 0.5 percent) to an eye. Subjects were assigned to one of three groups; either Paremyd OU, or Paremyd OS and tropicamide (either 0.5 or 1.0 percent) OD, or Paremyd OD and tropicamide OS. Pupillary dilation was measured during BIO performed at a set illumination using a near point card. RESULTS: Results indicate that Paremyd is a significantly more effective dilator than either concentration of tropicamide alone. BIO was rated good to excellent for all dilating agents. As could be expected (based upon data from previous experiments), there was a small, but significant, negative correlation between dilation and age, skin pigmentation, and iris pigmentation. CONCLUSIONS: Paremyd, because of its superior effect upon dilation without side effects, can be the preferred agent used for routine single-drop dilation in all patients, independent of age, iris color, or skin color.

Adolescent↗

PubMed1995

Lack of interaction between fluvastatin and oral hypoglycemic agents in healthy subjects and in patients with non-insulin-dependent diabetes mellitus.

Human drug interaction studies in vivo are conducted when in vitro and/or animal interactions suggest clinical relevance. Studies in vitro have indicated that the new, entirely synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin affects the metabolism of the nonsteroidal anti-inflammatory drug diclofenac and the oral hypoglycemic tolbutamide. Diclofenac and tolbutamide are both model substrates of the CYP2C isozymes, suggesting that this enzyme could be involved in the underlying mechanism of interaction. The concomitant use of lipid-lowering drugs with oral hypoglycemic agents has been recommended in patients with non-insulin-dependent diabetes mellitus (NIDDM). Therefore, 2 studies were initiated to explore potential pharmacokinetic and pharmacodynamic interactions between fluvastatin, simvastatin, or placebo and the oral hypoglycemic agents tolbutamide (study I) and glyburide (study II), each in 16 healthy subjects. These compounds were selected because of a demonstrated in vitro interaction with tolbutamide and widespread clinical use of glyburide. A further study (study III) was conducted to investigate the potential pharmacokinetic and pharmacodynamic interactions between fluvastatin and glyburide under therapeutic conditions in 32 patients with NIDDM. Single and multiple coadministration of fluvastatin 40 mg or simvastatin 20 mg increased the mean maximum plasma concentration and area under the concentration-time curve of glyburide by about 20%. The pharmacokinetics of tolbutamide were influenced to only a minor extent. Fluvastatin concentration-time profiles were unaffected by tolbutamide or glyburide coadministration. However, the pharmacokinetic interactions between fluvastatin or simvastatin and tolbutamide and glyburide were not associated with clinically relevant changes in blood glucose and insulin concentrations and, therefore, are not considered to be relevant in therapeutic practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1995

Modelling of the pharmacodynamic interaction of an A1 adenosine receptor agonist and antagonist in vivo: N6-cyclopentyladenosine and 8-cyclopentyltheophylline.

1. The purpose of this investigation was to develop a pharmacokinetic-pharmacodynamic model for the interaction between an adenosine A1 receptor agonist and antagonist in vivo. The adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA) and the antagonist, 8-cyclopentyltheophylline (CPT) were used as model drugs. The CPA-induced reduction in mean arterial pressure and heart rate were used as measurements of effect. 2. Four groups of eight rats each received 200 micrograms kg-1 of CPA i.v. in 5 min during a steady-state infusion of CPT at a rate of 0, 57, 114 or 228 micrograms kg-1 h-1. The haemodynamic parameters were continuously measured and frequent blood samples were taken to determine the pharmacokinetics of the drugs. 3. CPT had no influence on the pharmacokinetics of CPA and the baseline values of the haemodynamic variables. Furthermore, no clear antagonism by CPT was observed of the CPA-induced reduction in mean arterial pressure. However, CPT antagonized the effect on heart rate, and with increasing CPT concentrations, a parallel shift of the CPA concentration-effect relationship to the right was observed. 4. An agonist-antagonist interaction model was used to characterize the interaction quantitatively. On the basis of this model, the pharmacodynamic parameters of both CPA and CPT could be estimated. For CPA the values were (mean +/- s.e.): Emax = 198 +/- 11 b.p.m., EC50 = 2.1 +/- 0.7 ng ml-1, Hill factor = 2.3 +/- 0.6 and for CPT: EC50 = 3.7 +/- 0.3 ng ml-1 and Hill factor = 3.1 +/- 0.1. 5. It is concluded that the competitive agonist-antagonist interaction model may be of value to characterize quantitatively the pharmacodynamic interactions between adenosine A1 receptor ligands in vivo.

Adenosine↗

PubMed1994

Pneumonia in the surgical intensive care unit. Immunologic keys to the silent epidemic.

OBJECTIVE: The authors undertook a prospective study of trauma victims in the intensive care unit (ICU) to investigate the clinical course of pneumonia and the local and systemic immune responses to the pneumonia. SUMMARY BACKGROUND DATA: The silent epidemic of pneumonia has been an "unappreciated killer" in terms of being overlooked in surgical ICUs for the past 5 years, and specifically, the most common major infection after severe trauma. Little is known about the immune response to an acute pulmonary infection. METHODS: The authors studied 50 consecutive, critically ill trauma patients, with a mean injury severity score of 28 +/- 2, who developed pneumonia while ventilated mechanically. Patients were observed clinically, and specific immunologic parameters, including major histocompatibility antigen HLA-DR, complement receptor (CR3), and Fc receptor (FcRIII), were measured in circulating and local alveolar leukocytes for up to 30 days. Eleven patients provided unique clinical data via bronchoscopy for unilateral pneumonia, with collection of bronchoalveolar lavage (BAL) fluid from both the infected and uninfected sides. RESULTS: Patients developed clinical pneumonia 5.3 +/- 0.4 days after admission to the ICU. At diagnosis, mean temperature was 101.4 F, white blood cell count was 16,000/mm3, arterial oxygen tension was 104 +/- 14, fraction of inspired oxygen was 0.47, and positive end-expiratory pressure was 5. Thirty patients (Group A) recovered relatively promptly; 20 patients had prolonged illnesses (Group B), 15 of whom ultimately survived, and five of whom died. Patients with poor outcomes had greater leukocytosis (p < 0.05) and temperature elevation (p < 0.05) after 5 days of pneumonia. Immunologically, peripheral leukocyte expression of HLA-DR, FcRIII, and CR3 was equivalent in both groups. However, the expression of all three antigens on local alveolar leukocytes was decreased to a greater extent in the poor outcome group compared to the good outcome group, evident before any clinical differentiation between the two outcome groups. CONCLUSIONS: Pneumonia prolonged duration of mechanical ventilation, ICU and hospital stay, and overall infectious morbidity. Although immune suppression has been recognized as a result of initial injury, the development of pneumonia coincided with the nadir of immune function. Poor outcome patients were clinically identifiable 5 days after pneumonia and immunologically identifiable within 2 days. Moreover, there was localized suppression of pulmonary leukocytes at the site of the infiltrate compared to the uninfected lobes. This same alteration was noted in experimental Klebsiella pneumoniae pneumonia. This evidence suggests that there is active immune participation within the respiratory system. It also suggests that there are predispositions to pulmonary infections, and it may allow immune modulation targeted to pulmonary leukocytes to hasten clinical recovery and minimize pulmonary dysfunction.

Adult↗

PubMed1993

IgG from amyotrophic lateral sclerosis patients increases current through P-type calcium channels in mammalian cerebellar Purkinje cells and in isolated channel protein in lipid bilayer.

The effect of the IgG from amyotrophic lateral sclerosis (ALS) patients was tested on the voltage-dependent barium currents (IBa) in mammalian dissociated Purkinje cells and in isolated P-type calcium channels in lipid bilayers. Whole cell clamp of Purkinje cells demonstrates that ALS IgG increases the amplitude of IBa without modifying their voltage kinetics. This increased IBa could be blocked by a purified nonpeptide toxin from Agelenopsis aperta venom (purified funnel-web spider toxin) or by a synthetic polyamine analog (synthetic funnel-web spider toxin) and by a peptide toxin from the same spider venom, omega-Aga-IVA. Similar results were obtained on single-channel recordings from purified P channel protein. The addition of ALS IgG increased single-channel IBa open time without affecting slope conductance. The results described above were not seen with normal human IgG nor with boiled ALS IgG. It is concluded that ALS IgG enhances inward current through P-type calcium channels. Since P-type Ca2+ channels are present in motoneuron axon terminals, we propose that the enhanced calcium current triggered by ALS IgG may contribute to neuronal damage in ALS.

Amyotrophic Lateral Sclerosis↗