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Biomedical subjects

R C Read

Publications and source records attributed to R C Read.

At least 55 records · Page 3Linked to original sources

The (alpha2-->8)-linked polysialic acid capsule of group B Neisseria meningitidis modifies multiple steps during interaction with human macrophages.

Group B Neisseria meningitidis causes systemic disease, including meningitis, after initial colonization and subsequent penetration of nasopharyngeal mucosa, a tissue which is richly populated by macrophages. In an initial effort to characterize the interaction of N. meningitidis and mature human macrophages, the influence of the alpha2-->8) -linked polysialic acid capsule on the interaction of N. meningitidis with human monocyte-derived macrophages was investigated with a capsulate case isolate and an isogenic Tn916-derived noncapsulate transformant. The capsulate strain was fourfold less adherent to the macrophage surface after cold incubation, although adherence of both strains was significantly increased after opsonization with nonimmune C5-depleted serum. When opsonized inocula were adjusted so that they adhered to macrophages in equal numbers, the two strains were internalized at equivalent rates and both entered membrane-bound compartments (phagosomes). Colocalization of bacteria with the late endosomal and lysosomal marker lysosome-associated membrane protein revealed that fusion of lysosomes with phagosomes containing the capsulate organism was significantly reduced 10 and 30 min after entry, but by 1 h, no difference between the strains was observed. Once internalized, meningococci were effectively killed, although more rapid killing of the capsulate strain was observed over the first 3 h. These results indicate that the (alpha2-->8)-linked polysialic acid capsule modifies the interaction of meningococci with human macrophages at multiple steps, including adherence to the macrophage surface and phagosome-lysosome fusion. Moreover, the discordance between the kinetics of phagosome- lysosome fusion and bacterial killing suggests that a nonlysosomal mechanism may be responsible for a significant fraction of macrophage killing of N. meningitidis.

Antigens, CD↗

Second primary lung cancer.

We reviewed our experience with second primary lung cancer (SPLC) at the Little Rock Veterans Affairs Medical Center from 1966 to 1993. Fifty-four patients were found to have 65 such lesions after 1,572 "curative" resections for lung cancer (4.1%). Eleven patients had at least a third primary tumor (3 having more). Metachronous SPLCs comprised 60% (39/65) and synchronous 40% (26/65). The mean interval between first and second tumors was 54.63 +/- 8 (standard error) months (range, 5 to 218 months), and that between second and third was 26.1 +/- 7.4 (standard error) (range, 5.5 to 51 months). Squamous cell carcinoma comprised 58.4% (38/65), adenocarcinoma 30.8% (20/65), and small cell carcinoma 10.8% (7/65). Histology of the SPLC was the same as that of the first tumor in 50.7% (33/65). Stage I primary tumors comprised 76% (41/54) of index tumors, 61.1% (33/54) of SPLCs, and 72.2% (8/11) of third primary tumors. Second primary lung cancer followed minimal resection in 44% (24/54), lobectomy in 37% (20/54), and pneumonectomy in 13% (7/54) of cases. There was no evidence that minimal resection for the first primary tumor predisposed to SPLC. After 1983 the majority of SPLCs were diagnosed with computed tomographic scanning. After resection of SPLCs, survival rates at 3 and 5 years were 26% and 18%, metachronous 39% and 23.4%, and synchronous 12.25% and 12.25%.

Actuarial Analysis↗

Evolution of pulmonary resection techniques and review of the bronchus-first method.

The dissection technique of pulmonary resection evolved in the period 1930 to 1950. Surgeons had to cope with the location of disease, bronchiectasis, tuberculosis, and lung cancer, as well as associated bronchial secretions, hilar pathology, and the status of anesthesiology. Two basic hilar dissection methods emerged, the anterior vessel-first sequence and the posterior bronchus-first method. The bronchus-first method is particularly suitable for pneumonectomy, right upper lobectomy, and posterior-apical segmentectomy of this lobe as well as ease of lymph node removal. This technique, as a primary method of lung resection, does not appear to be emphasized in teaching curricula and supporting atlases or texts.

Dissection↗

Prolonged cryptosporidiosis during primary HIV infection.

Primary infection with the human immunodeficiency virus causes profound immunosuppression with a decrease in lymphocyte numbers and function. However, this immunosuppression is transient and most individuals regain normal immune function. Infection with opportunist pathogens during the period of immunosuppression is rare. We report a case of severe prolonged cryptosporidiosis complicating primary HIV infection. This has not previously been described. A review of other cases of opportunist infections in primary HIV infection suggests that various pathogens may take advantage of the transient immunosuppression. This has important implications for the diagnosis and management of acute HIV infection, and for the diagnostic criteria currently used for AIDS.

AIDS-Related Opportunistic Infections↗

Experimental infection of human nasal mucosal explants with Neisseria meningitidis.

The interaction of Neisseria meningitidis with rhinopharyngeal epithelium was studied by experimental infection of explants of human nasal turbinate mucosa with two wild strains: a fully capsulate case isolate, and an epidemiologically related non-capsulate nasopharyngeal isolate. After incubation for 4 h, epithelial cells of infected explants changed conformation from tall columnar morphology towards cuboidal, and there was increased discharge of mucus globules from goblet cells. By 24 h there was significant damage to infected epithelia, including projection of cells out of the surface, cytoplasmic blebbing and mitochondrial abnormalities. Meningococci were associated with surface non-ciliated cells by 4 h after infection. By 24 h after infection they were associated extensively with all cell types exhibiting damage. There was little association with secreted mucus. In areas of cell damage, penetration between surface cells was observed. Endocytosis into non-ciliated cells was observed in only a minority of explants studied and only in those infected for 24 h. From this intracellular site there was apparent migration to adjacent cells and to intercellular locations. No organisms were observed within or beneath basement membrane collagen in any explants but internalisation into mononuclear phagocytes was observed occasionally.

Cilia↗

Diagnostic and management problems in a complex case of connective tissue disease.

A 28-year-old Nigerian woman presented with persistent pyrexia, marked pruritus, eosinophilia, myalgias, flitting arthralgias, serositis and massive splenomegaly. Intensive investigation for an infective or neoplastic aetiology proved negative. Empirical treatment for helminthic infections and tuberculosis was unhelpful. Although there were no specific clues to suggest an underlying connective tissue disease, a trial of steriods and azathioprine was introduced, with no obvious response. Her condition deteriorated to a point where it was decided that intravenous immunosuppressive therapy was needed and subsequently, her condition improved remarkably. This patient illustrates the problems in the diagnosis and management of complex disorders, particularly when classical tests for connective tissue diseases are absent. Also, we would like to report that marked pruritus can be associated with connective tissue disease.

Adult↗

Interaction of fimbriated and nonfimbriated strains of unencapsulated Haemophilus influenzae with human respiratory tract mucus in vitro.

Adherence to mucus may influence bacterial colonization of the respiratory tract. Clinical isolates of nontypable Haemophilus influenzae (NTHi) from the respiratory tract are often fimbriated. We wondered whether fimbriated strains have a different adherence from related nonfimbriated strains. A microtitre plate assay has been developed to study adherence of nontypable H. influenzae to mucus. Wells were coated by incubation either with sol phase of sterile mucoid secretions or with purified preparations of mucins. Two laboratory pairs of fimbriated (F+) and nonfimbriated (F-) nontypable H. influenzae, and six fresh clinical isolates of fimbriated nontypable H. influenzae each with nonfimbriated partners derived by serial passage on agar, were cultured to mid-log phase, washed, and then added to the wells. They were then incubated at 37 degrees C for 30 min before washing to remove unbound bacteria. Adherent bacteria were desorbed by agitation with 0.5% Tween 80 and a viable count performed. The two fimbriated laboratory strains (n = 12 and n = 17), and 5 of the 6 fimbriated clinical isolates were more adherent to sol phase than their respective nonfimbriated partners. Two nonfimbriated clinical isolates were more adherent to plastic than their fimbriated partners. A fimbriated laboratory strain was more adherent than its nonfimbriated partner both to a purified preparation of high molecular mass mucin and to the glycopeptide fraction of the same. We conclude that fimbriated strains of nontypable H. influenzae have increased adherence to sol phase of mucus and purified human respiratory tract mucin. The interactions of fimbriae with mucus are likely to be complex, and may involve both nonspecific and specific interactions.

Bacterial Adhesion↗

Carotid-subclavian bypass: a twenty-two-year experience.

PURPOSE: A retrospective review of 124 patients who underwent carotid-subclavian bypass from 1968 to 1990 was done to assess primary patency and symptom resolution. METHODS: Preoperative data included age, atherosclerosis risk factors, and indications for surgery. Perioperative data included mortality and morbidity rates and graft conduit. Postoperative follow-up assessed graft patency, resolution of symptoms, and late survival. RESULTS: Age ranged from 42 to 78 years (mean 57.9). Indications for surgery were vertebrobasilar insufficiency in 24 (19%), extremity ischemia (EI) in 33 (27%), transient ischemic attacks (TIAs) in 13 (11%), both vertebrobasilar insufficiency and EI in 31 (25%), and both TIAs and EI in 23 (18%) patients. Graft conduits were polytetrafluoroethylene in 44 (35%) and Dacron in 80 (65%) cases. Concomitant ipsilateral carotid endarterectomy was done in 32 (26%) patients. During operation, death occurred in one patient (0.8%), and complications occurred in 10 (8%) patients. Thirty-day primary patency and symptom-free survival rates were 100%. Long-term follow-up ranging from 5 to 164 months was available for the 60 cases done between 1975 and 1990. Three grafts occluded at 30, 36, and 51 months after surgery for a primary patency rate of 95% at 5 and 10 years. Twenty-two patients died, yielding survival rates of 83% at 5 years and 59% at 10 years. Symptom recurrence occurred in six (10%) patients from 9 to 66 months after surgery. The symptom-free survival rate was 98% at 1 year, 90% at 5 years, and 87% at 10 years. Symptoms recurred in three patients with occluded grafts and three with patent grafts. The preoperative symptoms of drop attacks and TIAs did not recur. EI recurred in 5% and was noted only in the presence of graft occlusion. Dizziness recurred in 17% of patients admitted with this symptom and was observed despite graft patency. CONCLUSION: Carotid-subclavian bypass was a safe and durable procedure for relief of symptomatic occlusive disease of the subclavian artery. Long-term symptomatic relief appeared particularly likely in patients with drop attacks or upper extremity ischemia.

Adult↗

Isolated symptomatic midcervical stenosis of the internal carotid artery.

All carotid arteriograms performed between January 1, 1986 and December 31, 1991 were reviewed for instances of midcervical carotid stenosis. Sixteen cases were identified. A stenosis related to the hypoglossal nerve was specifically identified in three operative reports in the retrospective review. Pathologic examinations of the specimens confirmed the presence of atherosclerotic plaque or fibrous dysplasia. In another case, relief of intermittent neurologic symptoms (TIAs) was obtained by division of the stylohyoid ligament. Prospective observation of five cases confirmed a stenosis immediately distal to a transverse neurofascial band formed by the hypoglossal nerve, which arose with the vagus nerve in three patients, and a large cervical contribution to the ansa hypoglossi in two. Presumably the lesion was caused by the turbulent flow in the internal carotid artery distal to the band. Isolated stenosis of the midcervical internal carotid artery unrelated to bifurcation disease may be the result of turbulence induced by tethering neural or myofascial bands.

Aged↗

The concentrations of clarithromycin and its 14-hydroxy metabolite in sputum of patients with bronchiectasis following single dose oral administration.

Clarithromycin and its metabolite, 14-hydroxy-clarithromycin are active against a wide range of respiratory pathogens. Antibiotics generally penetrate poorly into respiratory secretions which may therefore continue to harbour bacteria following bronchial infection. We have studied sputum and serum concentrations of clarithromycin and 14-hydroxy-clarithromycin in eight patients with idiopathic bronchiectasis without infective exacerbations (five male, three female; mean age 53.3 years). Oral single dose administration of 250 or 500 mg clarithromycin, separated by at least 6 days, was given to each patient. Serum and sputum samples were collected (the latter by physiotherapy at 0, 1, 2, 4, 8, 24 and 0, 4, 8 and 24 h respectively after administration of each dose. Serum sol phase was obtained by high speed centrifugation and concentrations of clarithromycin and 14-hydroxy-clarithromycin were determined by high performance liquid chromatography. Serum Cmax for clarithromycin and 14-hydroxy-clarithromycin were 1.20 mg/L (3 h) and 0.37 mg/L (3.1 h) for clarithromycin (250 mg)) and were 2.78 mg/L (2.5 h) and 0.68 mg/L (2.6 h) for clarithromycin (500 mg) respectively. Sputum Cmax for clarithromycin and 14-hydroxy-clarithromycin were 0.52 mg/L (5 h) and 0.30 mg/L (5.5 h) for clarithromycin (250 mg) and were 1.59 mg/L (5 h) and 0.47 mg/L (5.5 h) for clarithromycin (500 mg) respectively. The sputum/serum percentage ratios at Cmax (sputum) for clarithromycin and 14-hydroxy-clarithromycin were 74.3% and 113.9% (250 mg) and 94.7% and 99.9% (500 mg) respectively. We conclude that oral administration of clarithromycin to patients with bronchiectasis results in rapid penetration into respiratory mucus with persistent drug concentrations that exceed its MIC for many respiratory pathogens.

Administration, Oral↗

An in vitro model for measuring tryptase release from nasal mucosa in response to allergen challenge.

A simple in vitro nasal mucosal culture model has been developed to measure release of the mast cell specific enzyme tryptase in response to allergen challenge. Patients who were undergoing inferior turbinectomy were skin-tested for commonly inhaled allergens. The mucosa from the inferior turbinates was kept viable using Minimal Essential Medium. Tryptase release into the medium was measured using the Pharmacia Riact Assay. There was a significant increase in tryptase release in response to allergen challenge from the mucosa harvested from skin-test positive patients. Mucosa from skin-test negative patients failed to demonstrate an increase in tryptase release. This could prove to be a useful research model for the study of nasal type I hypersensitivity and drugs that affect it.

Allergens↗

Pulmonary artery sleeve resection for abutting left upper lobe lesions.

Because the left upper lobe bronchus overlies the left pulmonary artery (PA), T2-3 lesions, N0-1 disease, or rarely inflammation may involve this vessel, necessitating lobectomy with partial PA resection or pneumonectomy with sacrifice of the lower lobe. In 486 operations performed for left upper lobe lesions between 1966 and 1992 (wedge, 111; segmentectomy, 131; lobectomy, 155; pneumonectomy, 89), isolated PA encroachment was caused by bronchogenic carcinoma (32), invasive aspergillosis (2), or organized pneumonitis (1) and occurred in 9% (32/360) of malignant left upper lobe tumors and 2% (3/126) of benign lesions. Initially (1966 through 1979), PA involvement was the indication for 30% (18/60) of left pneumonectomies. Later (1980 through 1990), tangential resection of the PA was attempted in 11, 5 ending up with pneumonectomy. Overall, 35 of 244 patients undergoing major left upper lobe resection (lobectomy or pneumonectomy) had PA encroachment. Recently, we have performed, selectively in patients with restricted lung function, six left upper lobectomies with sleeve resection of the PA. Paneled saphenous vein interposition was used (3) or 18-mm polytetrafluorethylene tube prostheses (3). All patients survived, 1 later requiring completion pneumonectomy for bronchostenosis after wedge bronchoplasty. Two have since died of metastases or pulmonary insufficiency; the remainder (average follow-up, 17 months) are asymptomatic with lower lobe function in 3 confirmed by differential ventilation-perfusion scans and pulmonary angiography.

Adult↗

Thromboembolism in patients undergoing thoracotomy.

To determine the incidence of thromboembolism in relation to thoracotomy, 77 patients undergoing pulmonary resection were prospectively studied up to 30 days postoperatively for deep venous thrombosis and pulmonary embolism. Overall, 20 of 77 patients (26%) had thromboembolic events during their hospitalization. Four deep venous thromboses and 1 pulmonary embolism were detected in 5 of 77 patients preoperatively for an incidence of 6%. Postoperative thromboembolism was detected in 15 of 77 (19%): deep venous thrombosis in 11 (14%) and pulmonary embolism in 4 (5%). No postoperative thromboembolisms occurred in the 17 patients receiving preoperative aspirin or ibuprofen, whereas they did occur in 25% of the remainder (15/60). Thromboembolism after pulmonary resection was more frequent with bronchogenic carcinoma than with metastatic cancer or benign disease (15/59 [25%] versus 0/18 [0%]; p < 0.01), adenocarcinoma compared with other types of carcinoma (11/25 [44%] versus 4/34 [12%]; p < 0.0004), large primary lung cancer (> 3 cm in diameter) compared with smaller lesions (9/19 [47%] versus 6/40 [15%]; p < 0.0001), stage II compared with stage I (7/14 [50%] versus 7/34 [21%]; p < 0.04), and pneumonectomy or lobectomy compared with segmentectomy and wedge resection (14/49 [29%] versus 1/28 [4%]; p < 0.005). Three of 4 patients with thromboembolism detected preoperatively had operation within the previous year. Postoperative pulmonary embolism was fatal in 1 of 4 (25%) and accounted for the one death. These results suggest patients undergoing thoracotomy for lung cancer, especially adenocarcinoma, should be considered for thromboembolic prophylaxis.

Adenocarcinoma↗

Properitoneal prosthetic placement through the groin. The anterior (Mahorner-Goss, Rives-Stoppa) approach.

The operative technique presented here, placement of polypropylene mesh in the properitoneal (deep) position through an inguinal approach, has yielded very satisfactory results with few recurrences and with postoperative morbidity rates comparable to those of standard techniques that do not involve prosthetic material. The main advantage of this method over other operations that utilize prosthetic material lies in the combination of the greater flexibility in the choice of operative technique afforded by the inguinal approach and the potential benefit of low recurrence rates after properitoneal placement of the mesh. There is an urgent need for a controlled randomized trial addressing the potential benefit (or lack thereof) of hernia repairs with prosthetic material in general, as well as the issue of optimal placement of the prosthesis.

Adult↗

Haemophilus influenzae infection of human respiratory mucosa in low concentrations of antibiotics.

We examined the effects of 0.25 and 0.5 minimal inhibitory concentrations (MIC) of amoxicillin, loracarbef, and ciprofloxacin on the interaction of a clinical isolate of nontypable Haemophilus influenzae (NTHi) with human adenoid organ culture. Adenoid tissue was embedded in agar so that only the mucosal surface was exposed. Minimum essential medium containing NTHi with or without antibiotics was added to the organ culture and incubated with 5% CO2 at 37 degrees C for 24 h. The organ cultures (n = 6) were assessed for several parameters by light microscopy (LM) and transmission electron microscopy (TEM). Bacterial viable counts after 24 h were not significantly different in all organ cultures. Compared with uninfected controls at 24 h, infection with NTHi caused significant (p < 0.05) damage to epithelium as assessed by LM: reduced ciliary beat frequency (CBF), disruption of epithelium integrity, and reduced number of ciliated sites. TEM showed extrusion of cells from the epithelial surface, loss of cilia from ciliated cells, cytoplasmic blebbing, and mitochondrial damage. In the presence of 0.25 and 0.5 MIC of all three antibiotics, the mucosal damage was significantly less (p < 0.05). We conclude that in the presence of sub-MIC levels of amoxicillin, loracarbef, and ciprofloxacin, NTHi infection causes less functional (CBF) and structural damage.

Adenoids↗