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Biomedical subjects

S H Harrison

Publications and source records attributed to S H Harrison.

At least 19 recordsLinked to original sources

Gangliosides as receptors for biological toxins: development of sensitive fluoroimmunoassays using ganglioside-bearing liposomes.

Gangliosides, glycosphingolipids present in the membranes of neuronal and other cells, are natural receptors for a number of bacterial toxins and viruses whose sensitive detection is of interest in clinical medicine as well as in biological warfare or terrorism incidents. Liposomes containing gangliosides mimic cells that are invaded by bacterial toxins and can be used as sensitive probes for detecting these toxins. We discuss detection of three bacterial toxins-tetanus, botulinum, and cholera toxins using ganglioside-bearing liposomes. Tetanus and botulinum toxins selectively bind gangliosides of the G1b series, namely, GT1b, GD1b, and GQ1b; and cholera toxin binds GM1 very specifically. Unilamellar liposomes containing GT1b or GM1 as one of the constituent lipids were prepared by extrusion through polycarbonate membranes. To impart signal generation capability to these liposomes, fluorophore-labeled lipids were incorporated in the bilayer of liposomes. The fluorescent liposomes, containing both a marker (rhodamine) and a receptor (GT1b or GM1) in the bilayer, were used in sandwich fluoroimmunoassays for tetanus, botulinum, and cholera toxins and as low as 1 nM of each toxin could be detected. The apparent dissociation constants of liposome-toxin complexes were in 10(-8) M range, indicating strong binding. This is the first report on detection of tetanus and botulinum toxins based on specific recognition by gangliosides. The fluorescent liposomes are attractive as immunoreagents for another reason as well--they provide enormous signal amplification for each binding event as each liposome contains up to 22,000 rhodamine molecules. The present approach using receptors incorporated in bilayers of liposomes offers a unique solution to employ water-insoluble receptors, such as glycolipids and membrane proteins, for sensitive detection of toxins and other clinically important biomolecules.

Bacterial Toxins↗

Size and duration of zidovudine benefit in 1003 HIV-infected patients: U.S. Army, Navy, and Air Force natural history data. Military Medical Consortium for Applied Retroviral Research.

OBJECTIVES: The study's objectives were to determine the size and duration of benefits of early versus delayed versus late treatment with zidovudine (ZDV) on disease progression and mortality in HIV-infected patients, and whether patients rapidly progressing before ZDV treatment had a different outcome from those not rapidly progressing before ZDV. DESIGN: The design was an inception cohort of 1003 HIV-infected patients. One hundred and seventy-four of the 1003 patients were treated before CD4 counts fell to <400 x 10(9)/L, ("early treatment"); 183 of 1003 patients were treated after CD4 counts fell to <400 x 10(9)/L but before clinical disease developed ("delayed treatment"); and 646 of the 1003 patients had either been treated after clinical disease developed or had not been treated at all by the end of follow-up ("late treatment"). Outcomes were progression to clinical HIV disease and mortality. RESULTS: The relative risk (RR) of progression for early versus delayed treatment was 0.58 (p < .03), and durability of ZDV benefits on progression was estimated at no more than 2.0 years; however, this estimate had wide confidence intervals. The RR of progression for delayed versus late treatment was 0.54 p < .0001, and durability of ZDV benefits was estimated at 1.74 years; this estimate had narrow confidence intervals. Survival was better for the early versus delayed treatment (RR = 0.55), but this difference was not statistically significant. In the subgroup of patients with more rapid CD4 decline prior to ZDV therapy, significant benefits on progression were observed for early versus delayed ZDV therapy (RR = 0.42, p = .02) and delayed versus late ZDV therapy (RR = 0.51; p = .0004). Duration of benefit was estimated to be 4.5 years (early versus delayed) and 1.7 years (delayed versus late). For patients with less rapid pre-ZDV decline in CD4 levels, a significant progression benefit was observed for delayed versus late therapy (RR = 0.50; p = .02). Duration of benefit in this subgroup was estimated to be 1.8 years. No significant benefit was found for early versus delayed treatment (RR = 1.12) in the less rapid pre-ZDV CD4 cell decline subgroup. CONCLUSIONS: Early treatment compared with delayed treatment was associated with a sizable reduction in HIV progression, but the duration of benefits was estimated to last only about 2 years. Delayed treatment compared with late treatment with ZDV was associated with substantial reduction of progression, but this reduction was also clearly limited in duration. Benefits on progression and mortality for the early treatment group were heavily dependent on the pre-ZDV CD4 slope. In the subgroup of patients with the most rapid pre-ZDV CD4 cell declines, the duration of benefit was much longer, possibly as long as 4 years.

Adult↗

Correlation between side of palpable tumor and side of pelvic lymph node metastasis in clinically localized prostate cancer.

Of 411 patients with palpable but clinically localized (Stages B or C) adenocarcinoma of the prostate, 100 (24.3%) were found at complete bilateral pelvic lymphadenectomy to have one or more lymph nodes positive for metastasis. These patients were divided into five subgroups on the basis of the location of the palpable tumor at digital rectal examination: left side only, left predominantly, both sides, right side predominantly, or right side only. Among 35 patients with positive nodes and a palpable tumor limited to one side of the prostate (clinically unilobar), metastases were found in the ipsilateral pelvic lymph nodes in 29 (83%). Only 6 (17%) of the patients had contralateral metastasis alone. A unilateral pelvic lymphadenectomy (ipsilateral to the side of the largest palpable tumor, or on either side if the tumor were bilateral) would have detected 80% of the patients with positive lymph nodes, with a positive predictive value of 100% and a negative predictive value of 94%. Lymph node metastases in patients with clinically localized palpable prostate cancer are most likely to be found on the same side as the palpable tumor and are considerably less likely to be found on the contralateral side alone. If frozen section examination of lymph nodes or laparoscopic lymph node dissection is planned before definitive therapy for prostate cancer, the pelvic lymph nodes ipsilateral to the side of the palpable tumor should be removed first.

Humans↗

Mallet finger.

Explore the source record for details and available documents.

Fingers↗

Skeletal surgery in the treatment of the rheumatoid hand.

Surgery of the rheumatoid hand is complex. It is important to understand the pathophysiology of deformity at the several linkaged joints of convexity of the wrist, metacarpophalangeal and interphalangeal joints. Pegging offers one of the best and reliable techniques of stabilising the joints. However, arthroplasty and soft tissue reconstruction play equally important roles in restoring hand function.

Adolescent↗

The "seagull" flap for syndactyly.

A technique is described for the treatment of post-burn syndactyly using a seagull shaped flap to produce a realistic commissure that does not subsequently advance distally. It can release volar digital contractures at the metacarpo-phalangeal level and import skin with tactile "adherence" into the distal palmar area.

Burns↗

The surgical management of the arthritic hand.

The surgical management of the arthritic hand is very largely concerned with rheumatoid arthritis and Still's disease and less frequently with psoriatic and degenerative arthritis. In the rheumatoid hand the surgeon may be called upon to intervene at any point in the chain reaction leading to total deformity, performing synovectomies of joints or tendons to relieve pain or prevent further deformity, repairing ruptured tendons, restoring the mechanism of injured joints, and correcting deformities when they have been allowed to occur. The great variety of operations that may be necessary to achieve these ends, with varying degrees of success, are discussed with reference to a personal series of 970 cases and 2002 operations.

Arthritis, Juvenile↗

The length of flexor tendon grafts.

The distance between the origin of the lumbrical muscle and the insertion of the flexor digitorum profundus tendon was measured at surgery in forty-eight patients. It was found that this distance was predictable and could be estimated without measurement prior to operation. A standard technique of flexor tendon grafting is described where this distance equals the length of the tendon graft.

Hand↗

Flexor synovectomy in the rheumatoid hand.

A review of the types, signs and symptoms of synovitis of the flexor surface of the hand. Indications, contra-indications and the results of surgery are discussed.

Arthritis, Rheumatoid↗