Biomedical subjects

J Haynes

Publications and source records attributed to J Haynes.

At least 37 records · Page 2Linked to original sources

PubMed1996

Erythro-9-(2-hydroxy-3-nonyl)adenine inhibits cyclic-3',5'-guanosine monophosphate-stimulated phosphodiesterase to reverse hypoxic pulmonary vasoconstriction in the perfused rat lung.

Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) was shown to reverse the hypoxic pressor response (HPR) in the isolated, blood-perfused rat lung model. EHNA, an adenosine deaminase inhibitor, showed reversal of the HPR in a dose-dependent manner (EC50 = 129 +/- 30 microM). We found that the reversal of HPR by EHNA was not mediated by the adenosine receptors because the EHNA effect was not blocked by the adenosine receptor antagonist, 8-p-sulfophenyl-theophylline (67 microM; n = 6). Pretreatment with a cy-clic-3',5'-adenosine monophosphate (cAMP)-dependent protein kinase inhibitor, Rp-adenosine-3',5'-cyclic monophosphorothioate (0.5 mM; n = 4), blocked EHNA reversal of the HPR. As an alternative mechanism of action, EHNA inhibition of cyclic nucleotide phosphodiesterase(s) isozymes was studied in endothelium intact and denuded pulmonary arteries. Using anion-exchange chromatography the cyclic nucleotide phosphodiesterase (PDE) separated into predominantly PDE families 2 and a mixture of 3 and 4. DEAE fractions showing cAMP hydrolysis activated by 5 microM cyclic-3',5'-guanosine monophosphate (cGMP) had a Km for cAMP of 6.3 microM and an apparent Kact for cGMP of 1.4 microM. EHNA was shown to inhibit PDE2 competitively. In intact vessels, the IC50 for EHNA was 3.3 microM using 0.03 microM [3H]-cAMP substrate assayed in the presence of 2 microM cGMP and in denuded vessels 3.7 microM at 0.03 microM [3H]-cAMP substrate in the presence of 5 microM cGMP. Fractions in which cAMP hydrolysis was inhibited or not affected by 5 microM cGMP (PDE3 and 4, respectively) showed an IC50 of > 200 microM for EHNA. We conclude that reversal of the hypoxic pressor response by EHNA in the isolated, perfused rat lung model occurs with a mechanism involving in part inhibition of smooth muscle PDE2.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1995

Prolongation of islet allograft survival with an antibody to vascular cell adhesion molecule 1.

BACKGROUND: The purpose of this study was to determine whether an antibody to vascular cell adhesion molecule 1 (VCAM1) prolongs the survival of neovascularized pancreatic islet allografts. METHODS: We treated CBA (H-2k) recipients of BALB/c (H-2d) islet allografts with anti-VCAM1 antibody (400 micrograms/day for 20 days). Sensitized recipients of islet grafts also were treated with anti-VCAM1. To study mechanism we performed mixed lymphocyte reactions (MLRs) with anti-VCAM1 and studied the graft infiltrate in treated recipients. RESULTS: Anti-VCAM1-treated CBA recipients showed prolonged graft survival with indefinite survival in five of nine cases. Anti-VCAM1 prevented proliferation in an MLR but not when added 36 hours after the beginning of the MLR. Anti-VCAM1 did not prolong allograft survival in sensitized recipients and did not prevent lymphocytic infiltration of the graft at 7 days. CONCLUSIONS: Anti-VCAM1 prolongs allograft survival in neovascularized islets in which the donor vascular endothelium plays little or no role in immunogenicity. VCAM1 appears to be important in the afferent phase (lymphocyte activation) of the allograft response. Once activated, either late in an MLR or in sensitized recipients, lymphocytes are not dependent on VCAM1 for function. Finally, anti-VCAM1 does not appear to affect the homing of lymphocytes to the allograft.

Animals↗

PubMed1995

Rheumatoid arthritis patients cannot accurately report signs of inflammatory activity.

If patients with rheumatoid arthritis (RA) could self-report symptoms in a manner which correlated with laboratory measures of inflammation this would be a valuable research or clinical tool. Developing such a tool means ensuring that the questions are understood and a variety of combinations of signs, symptoms and joints explored. Preliminary studies in two groups of 20 RA out-patients established an acceptable self-report questionnaire format by which patients could identify their joints. Fifty RA out-patients completed these self-report forms on four grades of each of four symptoms (pain, heat, stiffness, swelling) in each of 64 joints, as well as visual analogue scales (VAS) on overall pain and perceived disease activity. A clinical research assistant recorded the Thompson-Kirwan articular index (TKAI) and plasma viscosity (PV) was measured. The data were analysed in a variety of ways in an attempt to construct a self-report articular index (SRAI) which correlated with PV. The strongest models were then tested in 11 in-patients undergoing a flare of their disease. No adequate SRAI could be constructed which correlated with PV and in addition neither VAS score correlated with PV. There was a moderate correlation between the TKAI and a patient SRAI using the same joints, symptoms and weightings (r = 0.6, P < 0.01). Patients can clearly report different grades of multiple symptoms in multiple joints, but such reports cannot be shown to be a reliable indicator of inflammatory activity.

Arthritis, Rheumatoid↗

PubMed1995

Adenosine-induced vasodilation: receptor characterization in pulmonary circulation.

Adenosine mediates vascular smooth muscle relaxation in the pulmonary circulation. The A2 receptor has been suggested to mediate adenosine-induced vasodilation (AIV). In this study, the effect(s) of selective adenosine agonist and antagonist on the hypoxic pressor response (HPR) was assessed in the isolated blood-perfused rat lung. Adenosine (0.075-7.5 mM) infusion (0.125 ml/min) into the pulmonary artery dose dependently attenuated the HPR. AIV was mimicked by 10 microM 5'-(N-ethylcarboxamido)adenosine (NECA), a nonselective adenosine agonist. Adenosine- and NECA-induced vasodilation were attenuated by 67 microM 8-(p-sulfophenyl)theophylline. In contrast, NECA-induced vasodilation was not attenuated by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (1 microM). At 10 microM, a minimal vasodilatory effect was seen with the nonselective adenosine agonists CV-1808 and N6-(2-phenylisopropyl)adenosine (R-PIA) compared with NECA. The highly selective A2a agonist 2-[p-(2-carboxyethyl)phenyl amino]-5'-N-ethyl carboxamido adenosine (CGS-21680C, 10 microM) and A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 10 microM) had no vasodilatory effect. Neither the K+ channel blockers tetraethylammonium chloride (10 mM) and glibenclamide (100 microM) nor the NO synthase inhibitor N omega-nitro-L-arginine methyl ester attenuated NECA-induced vasodilation. These findings suggest that AIV is mediated via the A2b receptor and that AIV occurs via an NO-independent mechanism.

Adenosine↗

PubMed1993

Interaction of adriamycin aglycones with isolated mitochondria. Effect of selenium deficiency.

Adriamycin (AdM) aglycones have dramatic effects on isolated heart mitochondria, oxidizing pyridine nucleotides, modifying sulfhydryl groups, and triggering a permeability transition of the inner membrane that results in free passage of solutes smaller than 1500 Da. In this investigation, the role of glutathione (GSH) peroxidase in these actions of the aglycones was evaluated, by comparing mitochondria from selenium-deficient and selenium-supplemented rats, with the following results. Selenium deficiency was without effect on the permeability transition of heart mitochondria, followed via Ca2+ release and triggered by AdM aglycone or by t-butyl hydroperoxide (TBH) or H2O2, both of which are authentic substrates of the peroxidase. The permeability transition of liver mitochondria was delayed by selenium deficiency regardless of the triggering agent; however, substantial triggering by the aglycone and TBH persisted in mitochondria from selenium-deficient animals. Selenium deficiency inhibited thiol modification elicited by AdM aglycone and H2O2 in heart mitochondria and by the aglycone, TBH, and possibly H2O2 in liver mitochondria. It would thus appear that AdM aglycone, TBH, and H2O2 can induce the permeability transition of isolated heart mitochondria via a process (or processes) distinct from the catalytic activity of the peroxidase. Furthermore, even in liver, where involvement of the peroxidase is observed, mechanisms other than the GSH cycle can contribute to transition induction by the aglycone and by TBH. Finally, mitochondrial-SH group modification by the aglycones appeared not to be causally linked to induction of the permeability transition. This laboratory has suggested that the effects of aglycone metabolites of AdM on mitochondria mediate the cardiotoxicity that limits use of the parent drug. The data presented in this paper argue against the involvement of GSH peroxidase in that process. They are in agreement with in vivo studies, which have generally failed to find evidence for amelioration of AdM cardiotoxicity in selenium-deficient animals.

Animals↗

PubMed1993

Increasing awareness of arthritis--the public's response.

Six hundred and fifty telephone calls in response to a television programme about arthritis have been analysed for their content. Social and psychological isolation, lack of pain control and fears of side effects from tablets were the main concerns of callers. It is suggested that disease-orientated telephone help lines should be considered, and that future initiatives in public education should target some of the concerns expressed in this survey.

Adolescent↗

PubMed1993

The acute chest syndrome of sickle cell disease.

The acute chest syndrome (ACS), characterized by fever, chest pain, leukocytosis and a new infiltrate on chest roentgenogram, is a common complication of sickle hemoglobinopathies. The major differential diagnoses of ACS are pneumonia and pulmonary vaso-occlusive disease, which may occur simultaneously. Bacterial pulmonary infections are documented infrequently in ACS with the exception being in the pediatric population under 5 years of age. Because there are no clinical or laboratory parameters that clearly allow for distinction between pneumonia and vaso-occlusive disease, empiric use of antibiotics directed against S. pneumoniae and other pathogens commonly seen in community-acquired pneumonias remain a mainstay of therapy.

Acute Disease↗

PubMed1993

'In a dark time, the eye begins to see'.

In this paper I discuss a patient whose shadow became his rival, or as Jung put it, 'The shadow is lived'. I describe the beginning of a process of the assimilation of shadow contents, whereby the rupture between ego and shadow can no longer be maintained. I also discuss how it is primarily through the mutual experience and analysis of archetypal images that the unconscious contents become more integrated. In my clinical illustrations I also explore the relationship between my patient's fight with his shadow and his experiences of childhood shame. I consider how fear expressed through a panic attack may open a royal door to the unconscious, and the way in which its mediation through empathy and analysis can lead to unconscious infantile contents becoming more accessible. In addition, I show how, once some of the fear had subsided, it became possible for play to enter into the analysis.

Adult↗

PubMed1993

Microvascular hemodynamics in the sickle red blood cell perfused isolated rat lung.

In this study the effects of alveolar hypoxia on pulmonary microvascular hemodynamics in sickle red blood cell (HbSS-RBC) perfused rat lungs were studied under conditions of high and low oxygen tensions and compared with lung perfused with rat (HbRat) and normal human (HbAA) RBC controls. Independent of the RBC suspension (hematocrit 5%) used, ventilation with the room air gas mixture did not result in any significant differences in the pulmonary arterial pressure (Ppa), capillary pressure (Ppc), total pulmonary vascular resistance (RT), or angiotensin II pressor response. Ventilation of HbSS-RBC perfused lungs with a hypoxic gas mixture significantly increased the Ppa, Ppc, and RT above that which was seen in HbRat and HbAA controls. The increase in RT occurred mainly in the pulmonary artery independent of RBC suspension. In addition, no significant accumulation of lung water occurred in HbSS-RBC perfused lungs compared with HbRat and HbAA controls, as indicated by the change in capillary filtration coefficient and wet-to-dry lung weight ratio. In conclusion, deoxygenation of the HbSS-RBC and hypoxic pulmonary vasoconstriction is additive in altering pulmonary microvascular hemodynamics.

Anemia, Sickle Cell↗

PubMed1993

Ischemia-reperfusion injury in the isolated rat lung. Role of flow and endogenous leukocytes.

Microvascular lung injury caused by ischemia-reperfusion (IR) may occur via leukocyte-dependent and leukocyte-independent pathways. Leukocyte-endothelial adhesion may be a rate-limiting step in IR lung injury. Leukocyte adhesion to microvascular endothelium occurs when the attractant forces between leukocyte and endothelium are greater than the kinetic energy of the leukocyte and the vascular wall shear rate. We hypothesized (1) that isolated, buffer-perfused rat lungs are not free of endogenous leukocytes, (2) that endogenous leukocytes contribute to IR-induced microvascular injury as measured by the capillary filtration coefficient (Kfc), and (3) that a reduction of perfusate flow rate would potentiate leukocyte-dependent IR injury. Sixty lungs were divided into four groups: (1) low-flow controls, (2) high-flow controls, (3) low-flow IR, and (4) high-flow IR. Microvascular injury was linearly related to baseline perfusate leukocyte concentrations at both low (r = 0.78) and high (r = 0.82) flow rates. Kfc in the high-flow IR group (0.58 +/- 0.03 ml/min/cm H2O/100 g) was less (p < 0.05) than Kfc in the low-flow IR group (0.82 +/- 0.07), and in both groups Kfc values were significantly greater than low-flow (0.34 +/- 0.03) and high-flow (0.31 +/- 0.01) control Kfc values after 75 min. Retention of leukocytes in the lung, evaluated by a tissue myeloperoxidase assay, was greatest in the low-flow IR group. We conclude (1) that isolated, buffer-perfused rat lungs contain significant quantities of leukocytes and that these leukocytes contribute to IR lung injury, and (2) that IR-induced microvascular injury is potentiated by low flow.

Analysis of Variance↗

PubMed1992

Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease.

Tazobactam is an irreversible inhibitor of many beta-lactamases. In combination with piperacillin, tazobactam exhibits synergy against many beta-lactamase-producing bacteria. The pharmacokinetics of piperacillin and tazobactam were evaluated in eight normal volunteers and in 52 patients with renal dysfunction. Plasma and urine were obtained for up to 30 hours after an infusion of piperacillin and tazobactam (3 and 0.375 gm, respectively). Dialysate samples were collected from patients undergoing dialysis. Piperacillin and tazobactam concentrations were determined by high-performance liquid chromatography. Noncompartmental methods were used for pharmacokinetic analysis. Piperacillin and tazobactam total body clearance, area under the curve, and terminal elimination rate correlated with renal function. Hemodialysis removed 31% and 39% of piperacillin and tazobactam, respectively. During continuous ambulatory peritoneal dialysis, 5.5% of the piperacillin and 10.7% of the tazobactam was recovered in the dialysate over 28 hours. Peak plasma concentrations of both drugs increased minimally with decreasing creatinine clearance. Dosage alterations for creatinine clearance values less than 40 ml/min are recommended.

Adult↗

PubMed1992

Role of cAMP-dependent protein kinase in cAMP-mediated vasodilation.

In this study, the role of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) in cAMP-dependent relaxation was assessed in the isolated-perfused rat lung using a PKA inhibitor, Rp-cAMPS, 8-bromo-cAMP (8-BrcAMP), and the diterpene activator of adenylate cyclase (AC), forskolin (FSK). A role for K+ channels was also assessed with the nonselective K+ channel blocker, tetraethylammonium (TEA, 10 mM), and an ATP-sensitive K+ channel inhibitor, glibenclamide (GLI, 100 microM). Both 8-BrcAMP (0.1-1.0 mM) and RSK (0.1-10 microM) dose-dependently attenuated the peak pressor response to alveolar hypoxia (HPR). Rp-cAMPS potentiated the HPR and attenuated 8-BrcAMP-mediated vasodilation but had no effect on FSK-mediated vasodilation. FSK-mediated vasodilation was not mimicked by 1,9-dideoxy-FSK, which is biologically inactive on AC but alters K+ channels identically to FSK, nor was it attenuated by the platelet-activating factor antagonist SRI 63-441 or the cyclooxygenase inhibitor indomethacin. TEA, but not GLI, attenuated FSK-mediated vasodilation. Similarly, TEA attenuated 8-BrcAMP-mediated vasodilation. These results support roles for PKA and indirect gating of a non-ATP-sensitive K+ channel in mediating cAMP-dependent pulmonary vasodilation.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1992

Reversal of increased microvascular permeability associated with ischemia-reperfusion: role of cAMP.

Ischemia-reperfusion (IR) is a form of oxidant injury known to increase microvascular permeability in the lung. Agents that increase adenosine 3',5'-cyclic monophosphate (cAMP) levels have been shown to have beneficial effects in several models of oxidant lung injury associated with increased microvascular permeability. We investigated the role of adenylate cyclase activation with isoproterenol (ISO) or forskolin (FSK) in reversing the increased microvascular permeability associated with IR. ISO or FSK administered after 45 min of ischemia and 46 min of reperfusion caused a reduction in the capillary filtration coefficient (Kfc) from 1.25 +/- 0.13 to 0.53 +/- 0.08 and 0.55 +/- 0.10 ml.min-1.cmH2O-1.100 g tissue-1, respectively, at 90 min of reperfusion. This reduction in Kfc was accompanied by a rise in perfusate cAMP levels from 16.5 +/- 4.9 and 31.2 +/- 11.9 pmol/ml at 45 min of reperfusion to 444.2 +/- 147.8 and 276.1 +/- 91.0 pmol/ml at 105 min of reperfusion in lungs treated with ISO or FSK, respectively, at 46 min of reperfusion. Dibutyryl cAMP (DBcAMP), a membrane-permeable cAMP analogue, mimicked the permeability effect by reducing Kfc to 0.67 +/- 0.15 at 90 min of reperfusion. Significant hemodynamic changes occurred but were small and cannot explain the observed effect on Kfc. Photomicrographs from lungs treated with ISO or FSK revealed a reversal of the morphological manifestations of increased microvascular permeability. We conclude that the increased microvascular permeability associated with IR can be reversed by ISO, FSK, and DBcAMP and that cAMP produced by the lung contributes to the observed reversal.

Animals↗

PubMed1992

Compounds that increase cAMP prevent ischemia-reperfusion pulmonary capillary injury.

This study evaluated the physiological effects of compounds that increase adenosine 3',5'-cyclic monophosphate (cAMP) on changes in pulmonary capillary permeability and vascular resistance induced by ischemia-reperfusion (I-R) in isolated blood-perfused rabbit lungs. cAMP was elevated by 1) beta-adrenergic stimulation with isoproterenol (ISO, 10(-5) M), 2) post-beta-receptor stimulation of adenylate cyclase with forskolin (FSK, 10(-5) M), 3) and dibutyryl cAMP (DBcAMP, 1 mM), a cAMP analogue. Vascular permeability was assessed by determining the capillary filtration coefficient (Kf,c), and capillary pressure was measured using the double occlusion technique. The total, arterial, and venous vascular resistances were calculated from measured pulmonary arterial, venous, and capillary pressures and blood flow. Reperfusion after 2 h of ischemia significantly (P less than 0.05) increased Kf,c (from 0.115 +/- 0.028 to 0.224 +/- 0.040 ml.min-1.cmH2O-1.100 g-1). These I-R-induced changes in capillary permeability were prevented when ISO, FSK, or DBcAMP was added to the perfusate at reperfusion (0.110 +/- 0.022 and 0.103 +/- 0.021, 0.123 +/- 0.029 and 0.164 +/- 0.024, and 0.153 +/- 0.030 and 0.170 +/- 0.027 ml.min-1.cmH2O-1.100 g-1, respectively). I-R significantly increased total, arterial, and venous vascular resistances. These increases in vascular resistance were also blocked by ISO, FSK, and DBcAMP. These data suggest that beta-adrenergic stimulation, post-beta-receptor activation of adenylate cyclase, and DBcAMP prevent the changes in pulmonary vascular permeability and vascular resistances caused by I-R in isolated rabbit lungs through a mechanism involving an increase in intracellular levels of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Hemoglobin potentiates oxidant injury in isolated rat lungs.

Isolated perfused rat lungs were subjected to oxidant injury induced by tert-butyl hydroperoxide (t-buOOH), which caused a significant increase in capillary permeability as assessed by the change in the capillary filtration coefficient. t-buOOH caused an increase in the change in the capillary filtration coefficient (delta Kfc) of 0.27 +/- 0.05 ml.min.cmH2O-1.100 g lung tissue-1 (mean +/- SE) that was accompanied by an increase in thiobarbituric acid reactive products of lipid peroxidation in the lung perfusate. The addition of hemoglobin to the perfusate potentiated t-buOOH-induced lung injury as evidenced by a significantly greater (P = 0.007) delta Kfc of 0.43 +/- 0.05. t-buOOH also caused hemoglobin to release large quantities of free iron in vitro. The potentiation of t-buOOH-induced lung injury by hemoglobin was prevented by apotransferrin as evidenced by a significant reduction (P = 0.001) in delta Kfc to 0.13 +/- 0.02. No statistically significant (P greater than 0.05) changes in segmental resistances or pulmonary vascular pressures occurred in any of the lungs injured with t-buOOH when compared with time controls. These results demonstrate that t-buOOH causes an oxidant injury in isolated rat lungs that can be potentiated by free iron released from hemoglobin.

Animals↗

PubMed1991

Selective inhibition of cGMP-inhibitable cAMP phosphodiesterase decreases pulmonary vasoreactivity.

Guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) are mediators of smooth muscle relaxation. In this study, selective inhibitors of phosphodiesterase (PDE) isozymes were used to assess the role of cyclic nucleotide hydrolysis in angiotensin II (ANG II) and hypoxic pulmonary vasoconstriction. In isolated rat lungs, the hypoxic pressor response (HPR) was induced with a 95% N2-5% CO2 gas mixture. When administered during the plateau of the HPR, trequinsin (nonselective PDE inhibitor) and indolidan (cGMP-inhibitable cAMP PDE inhibitor) significantly (P = 0.01) decreased the pulmonary arterial pressure (Ppa) by 60 +/- 7 and 53 +/- 3%, respectively, compared with zaprinast (cGMP PDE inhibitor), rolipram (cGMP-insensitive cAMP PDE inhibitor), and the 0.1% dimethyl sulfoxide (DMSO) vehicle control, which decreased the Ppa by 6 +/- 3, 4 +/- 3, and 0%, respectively. In the trequinsin and indolidan groups, the subsequent ANG II pressor responses and HPRs were significantly (P = 0.01) decreased when compared with the zaprinast, rolipram, and DMSO groups. During normoxia, none of the PDE inhibitor (0.3-30 microM) had an effect on the baseline Ppa. These results suggest that cAMP hydrolysis by the cGMP-inhibitable cAMP PDE play a significant role in pulmonary vascular tone regulation.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1991

Tuberculous pleural effusion. Twenty-year experience.

We reviewed the records of 1,738 cases of tuberculosis seen during the period from 1968 to 1988 in Mobile, Alabama. Seventy cases of tuberculous pleural effusion were identified and constituted 4.9 percent of all disease due to Mycobacterium tuberculosis during this period. Tuberculous pleural effusion was diagnosed if the patient had M tuberculosis cultured from sputum, pleura, or pleural fluid and had a roentgenographic pleural effusion without an alternative explanation for the presence of the effusion. The diagnosis of tuberculous pleural effusion was made in the absence of a positive culture if the patient had an undiagnosed lymphocytic exudative pleural effusion and all clinical and roentgenographic abnormalities resolved on antimycobacterial chemotherapy. The mean age of all patients was 47 +/- 18.4 years. The 70 cases were evenly divided between 35 that were accompanied by roentgenographic pulmonary parenchymal infiltrates and 35 that occurred in the absence of parenchymal infiltrates. We conclude that cultures of all potentially diagnostic specimens (sputum, pleural fluid, and pleura) and an intermediate-strength skin test, are sensitive tests for the diagnosis of tuberculous pleural effusion. In addition, the age of patients with tuberculous pleural effusion appears to be increasing.

Adult↗

PubMed1991

Results of bronchoscopically obtained lower airway cultures from adult sickle cell disease patients with the acute chest syndrome.

PURPOSE: The purpose of this study was to determine the frequency of bacterial pneumonia as a cause of the acute chest syndrome in adult patients with sickle cell disease based on bronchoscopically obtained lower airway cultures and to describe the clinical, laboratory, and roentgenographic features of the acute chest syndrome in a series composed entirely of adult patients with sickle cell disease. PATIENTS AND METHODS: We reviewed the hospital records from 19 episodes (18 patients) of acute chest syndrome in adult patients with sickle cell disease (greater than or equal to 19 years of age) who had undergone flexible bronchoscopy to obtain lower airway cultures between January 1979 and July 1987. We also recorded patients' clinical, laboratory, and roentgenographic characteristics. RESULTS: Pneumonia was diagnosed in four of 19 episodes (21%) of acute chest syndrome based on quantitative cultures obtained at bronchoscopy. The pneumonia was caused by Streptococcus pneumoniae in two patients and mixed aerobic and anaerobic organisms in the other two patients. Forty-four of 45 blood cultures were negative, and one grew Staphylococcus epidermidis, which was considered a contaminant. Chest roentgenograms revealed lower lobe involvement in 17 episodes (90%) and bilateral infiltrates in six (32%). Pleural effusions occurred in seven episodes (37%), and pleural fluid samples obtained from five of these revealed sterile exudates. CONCLUSION: The results of this retrospective study suggest that bacterial pneumonia is an uncommon cause of acute chest syndrome in adult patients with sickle cell disease. These results are consistent with previous retrospective studies using noninvasive techniques to diagnose pneumonia. Nevertheless, there appeared to be no reliable noninvasive variables that could accurately differentiate between patients with and without pneumonia and, consequently, we recommend empiric antibiotic therapy in addition to usual supportive care of these patients.

Adult↗