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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

Induction of beta2 integrin-dependent neutrophil adhesion to human alveolar epithelial cells by type 1 Streptococcus pneumoniae and derived soluble factors.

Pneumonia caused by Streptococcus pneumoniae is characterized by neutrophil infiltration and variable epithelial injury. Neutrophil adhesion to alveolar epithelial pneumocytes (A549) was measured and demonstrated to be dose-dependent following preincubation of these (A549) pneumocytes with type 1 S. pneumoniae. Adhesion peaked at a bacteria-to-epithelial cell ratio of 5:1 after a 4-h incubation but was absent after 2 h and without FMLP. Filtered conditioned media (CM) from pneumococci cultured with (CM+) or without (CM-) epithelial cells were tested. CM+ induced significant adhesion in the absence of FMLP (P < .001); CM- had no effect. In the presence of FMLP, adhesion induced by both media was significantly greater than by FMLP alone (P < .001) and was significantly blocked (P < .01) by antibodies to CD11b and CD18. CM+ upregulated epithelial intercellular adhesion molecule 1 but CM- did not. These data provide new information concerning the interactions of S. pneumoniae, alveolar epithelial cells, and neutrophils.

Alkaline Phosphatase↗

Experimental therapies for sepsis directed against tumour necrosis factor.

Tumour necrosis factor (TNF) has been identified as an important mediator involved in the generation of sepsis syndrome. Two major strategies have evolved for counteracting the effects of TNF in patients with severe manifestations of sepsis: neutralization by anti-TNF antibodies and competitive antagonism of TNF with synthetic soluble TNF receptors. Clinical trials with murine monoclonal antibodies against TNF have shown that this agent is able to reduce early morbidity and mortality, but with no reduction in 28 day mortality. A clinical study with a synthetic 75 kDa soluble TNF receptor failed to show any benefit with this drug and indeed there was higher mortality at higher doses. Trials of a 55 kDa soluble TNF receptor are continuing and this drug is apparently safe. Drugs that modify TNF in vivo may be a useful component of future management of sepsis, either as monotherapy or as part of a combined strategy of immunomodulation.

Antibodies, Monoclonal↗

Balloon dissection of the space of Bogros via the femoral canal for total extraperitoneal laparoscopic herniorrhaphy.

To obviate the need for general anesthesia or dissection of the rectus sheath, we have transferred laparoscopic herniorrhaphy back to the groin by first dissecting the suprainguinal parietoperitoneal space of Bogros via the femoral canal. Cadaver dissections demonstrated that the preperitoneal plane could be routinely fingered and distended with a digitally placed balloon introduced through a 1-cm incision immediately below the inguinal ligament. A 10-mm femoral laparoscopic port was then inserted and pressurized, allowing two standard 5-mm ports to be introduced from above, through the lower quadrant, under vision. The procedure was then carried out in the usual way, the mesh being inserted from below. Ten patients (two women), 23-73 years old, selected because general anesthesia was inadvisable, underwent uncomplicated prosthetic repair of unilateral (eight) or bilateral (two) inguinal defects. Half of the peritoneal sacs were pushed up and out of the inguinal canal; 18 months later there were no recurrences (inguinal or femoral). Preliminary experience with this new technique is promising. It may prove applicable to retroperitoneal exposure of the distal aorta and iliac vessels, allowing laparoscopic bypass for Leriche syndrome.

Abdomen↗

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↗