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Biomedical subjects

R A Mann

Publications and source records attributed to R A Mann.

At least 19 recordsLinked to original sources
PubMed1992

Differential effects of polyamine homologues on the prevention of DL-alpha-difluoromethylornithine-mediated inhibition of malignant cell growth and normal immune response.

Natural polyamines (putrescine, spermidine, and spermine) are ubiquitous cellular cations that play an important role in cell proliferation and differentiation. Ornithine decarboxylase is the first and a rate-limiting enzyme in the biosynthesis of polyamines. Polyamine depletion using DL-alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, has been shown to suppress cell growth in a variety of settings, including those of tumor and lymphocyte proliferation. The objective of the present investigation was to examine the inhibitory effects of DFMO on a variety of murine in vitro immune responses, including lymphocyte proliferation in response to T-cell mitogen (concanavalin A), B-cell mitogen (lipopolysaccharide), and alloantigen as well as cytotoxicity. DFMO-mediated inhibition of cell proliferation in these cases correlated with depletion of intracellular polyamines. The inhibitory effects of DFMO were reversed by polyamine repletion with putrescine. Putrescine also reversed the growth-inhibitory effects of DFMO on 4 tumor cell lines that we tested: 28-13-3S, YAC-1, P-815, and K562. However, putrescine homologues exhibited a differential effect in preventing DFMO-mediated inhibition of cell growth in normal lymphocytes and cancer cell lines. Only putrescine homologues containing a shorter methylene chain were effective in preventing the growth-inhibitory action of DFMO on normal immune response. In contrast, only the longer chain homologue 1,5-diaminopentane overcame the effect of DFMO on tumor cell growth. These findings suggest that supplementation with selected polyamine homologues may sustain normal immune response in DFMO-treated individuals while effectively suppressing malignant cell growth. The potential clinical relevance of these observations is discussed.

Animals↗
PubMed1992

Attenuation of murine acute lethal graft-versus-host disease by the administration of DL-alpha-difluoromethylornithine.

Intravenous injection of 5 x 10(7) C57BL/6 (B6) lymphocytes into adult (C57BL/6 x DBA/2)F1 recipient mice results in acute lethal graft-versus-host (ALGVH) disease. This disorder is characterized by anemia, a diminished number of splenocytes, impaired cytotoxicity (CTX) against third party alloantigen, and impaired natural killer cell (NK) activity. Parental anti-F1 CTX is critical to the induction of ALGVH disease, and CTX in general has been reported to be dependent upon the presence of the low molecular weight polyamines essential for cell growth and differentiation. We now report that DL-alpha-difluoromethylornithine, a specific inhibitor of polyamine biosynthesis, attenuates the clinical expression of disease in mice undergoing ALGVH disease.

Anemia↗
PubMed1992

Possible epidemiological factors associated with rupture of the posterior tibial tendon.

Rupture of the posterior tibial tendon has been postulated to occur, in part, as a result of degenerative changes to the tendon. This possibility was examined by a review of 67 patients (average age 57 years) diagnosed with rupture of the posterior tibial tendon. Forty-five of the 67 patients (60%) had one or more of the following positive medical histories: (1) hypertension, (2) obesity, (3) diabetes mellitus, (4) previous surgery or trauma about the medial aspect of the foot, or (5) steroid exposure. Thirty-five patients (52%) had either hypertension, diabetes mellitus, or obesity. A statistical correlation was demonstrated between rupture of the posterior tibial tendon and obesity (P = .005) and to a lesser extent hypertension (P = .025). These disorders have been uniformly associated with an acceleration of the degenerative processes associated with aging, commonly via an acceleration of microvascular and macrovascular diseases. An additional vascular risk is implicated by the known zone of hypovascularity of the posterior tibial tendon and risk of rupture secondary to systemic or local injections of corticosteroids. The prevalence of posterior tibial tendon rupture parallels the degenerative processes of aging, hypertension, diabetes mellitus, and obesity. Additionally, the effects of corticosteroids and local surgical procedures may further be associated with local vascular impairment and eventual rupture.

Adult↗
PubMed1992

The effects of recombinant human erythropoietin on the cell mediated immune response of renal failure patients.

Recombinant human erythropoietin (rHuEpo) is now widely employed in correction of the anemia of end stage renal disease (ESRD). Recent reports suggest that rHUEpo, in addition to its effect on CFU-E and burst-forming-unit-erythroid (BFU-E), may stimulate granulocyte/macro-phage production and pluripotential progenitors of the myeloid and monocyte lineage. Furthermore, there is now data which demonstrate that ESRD patients who received rHuEpo have enhanced cytokine production. Taken together, these observations suggest that the administration of rHuEpo may augment the diminished immune response of renal failure patients. To evaluate the effects of rHuEpo therapy on cell-mediated immunity in hemodialysis patients, a prospective controlled study was conducted. Two parameters of immune function were tested. One was natural killer cell (NK) activity, and the other proliferation in response to the T cell mitogen concanavalin A (Con-A). NK activity of the ESRD patients was comparable with that of normal controls at the start of the study and was unaffected by rHuEpo therapy. In contrast to this, anemic ESRD patients initially demonstrated impaired mitogen driven proliferation (initial stimulation index (S.I.) = 42.5 +/- 11.9) which significantly improved following rHuEpo therapy (final S.I. = 73.3 +/- 14.7, p < 0.05). The later value exceeded the mitogen response in less anemic ESRD patients who did not receive rHuEpo (initial S.I. = 60.7 +/- 16.5, final S.I. = 61.0 +/- 16.7), but did not reach values seen in normal controls. The data suggest that rHuEpo therapy may be associated with enhanced immune responses in patients with ESRD.

Aged↗
PubMed1992

Repair of hallux valgus with a distal soft-tissue procedure and proximal metatarsal osteotomy. A long-term follow-up.

We retrospectively reviewed the results for seventy-five patients (109 feet) in whom a hallux valgus deformity had been corrected with the release of the distal soft tissues, excision of the medial eminence, plication of the medial part of the capsule, and proximal crescentic osteotomy of the first metatarsal. The patients were followed for an average of thirty-four months (range, twenty-four to fifty-six months). The preoperative hallux valgus angle averaged 31 degrees, and the postoperative angle averaged 9 degrees. The preoperative intermetatarsal angle averaged 14 degrees and the postoperative angle, 6 degrees. Ninety-three per cent of the patients were satisfied with the result of the procedure. They stated that, given the same circumstances, they would have the operation again. The most common complication was hallux varus, which occurred in thirteen feet (nine patients). The other complications included recurrence of the hallux valgus in two feet, pain under a fibular sesamoid in one foot, and a tailor's bunion that was unrelated to the operation in one foot. Only five of forty-eight feet that had had a symptomatic plantar keratosis beneath the second metatarsal head preoperatively remained symptomatic postoperatively.

Adolescent↗
PubMed1991

Posttraumatic proximal migration of the first metatarsophalangeal joint sesamoids: a report of four cases.

Four cases are presented with plantar plate injury to the first metatarsophalangeal (MTP) joint and proximal retraction of the sesamoids by the flexor hallucis brevis. No history of dislocation occurred in any patient, although two had associated fractures of a sesamoid bone. Clinical and radiographic aids to the diagnosis are discussed. Clinical findings included diffuse pain beneath the first MTP joint and pain with extremes of joint motion in all patients. The anterior-posterior (AP) radiographic technique was the most helpful in determining the proximal migration of the sesamoids. By taking the AP view with both feet on the cassette and by centering the beam perpendicular to it, the diagnosis of plantar plate disruption can easily be made. Initial treatment of this disorder was nonoperative using a stiff soled shoe. With conservative treatment, two of the patients returned to preinjury activities. One patient required sesamoidectomy for resistant pain, and the final patient is still unable to return to his preinjury job requiring standing and heavy lifting.

Adult↗
PubMed1991

Hallux valgus repair. DuVries modified McBride procedure.

The DuVries modification of the McBride procedure was investigated in 72 feet in 47 patients with hallux valgus deformity. Overall, the patient satisfaction rate was 92%. The hallux valgus averaged 32 degrees preoperatively, and 16 degrees postoperatively. The intermetatarsal angle averaged 14 degrees preoperatively and 9 degrees postoperatively. Anatomic realignment of the remaining tibial sesamoid was achieved in 28% of the feet. As a result of realignment of the first metatarsophalangeal joint, the intractable plantar keratosis beneath the second metatarsal head was resolved in 19 of 20 feet. Six patients developed a hallux varus deformity that averaged 7.5 degrees. All cases of hallux varus had medial displacement of the tibial sesamoid. The number of patients who could withstand unrestricted shoe wear increased from ten patients preoperatively to 30 patients postoperatively. The patient activity level increased in two thirds of the cases. The distal soft-tissue procedure produces the most predictable correction in patients with a hallux valgus deformity measuring less than 30 degrees. In more severe deformities, a proximal metatarsal osteotomy should be added to the procedure.

Adolescent↗
PubMed1991

Chronic rupture of the Achilles tendon: a new technique of repair.

A new operative technique is described for the treatment of patients who have a rupture of the Achilles tendon. The large gap between the proximal and distal stumps of the Achilles tendon in seven patients was bridged by use of the tendon of the flexor digitorum longus as the graft. At the most recent follow-up examination (average follow-up, thirty-nine months; range, two to six years), the result was excellent or good in six patients and fair in one. Postoperatively, two patients needed an adjuvant procedure: one, a local rotation flap and the other, a split-thickness skin graft. Both patients had excellent restoration of function. The patient who had a fair result had a persistent limp and residual discomfort. There were no re-ruptures.

Achilles Tendon↗
PubMed1991

Ankle fusion.

Multiple techniques for ankle arthrodesis have been described. A transfibular lateral approach between the sural nerve and the lateral branch of the superficial peroneal nerve is utilized. This permits excellent visualization of the ankle joint so that correction of the deformity can readily be achieved under direct visualization. Eighteen ankle fusions carried out through a transfibular approach were reviewed. The fusion site was stabilized with two or more 6.5-mm AO screws. No bone graft was utilized. The follow-up period was from six to 48 months. Ages of the patients ranged from 21 to 68 years. The postoperative regimen was six weeks nonweight-bearing in a short-leg cast, followed by weight bearing in a short-leg cast until union occurred. All fusions but one healed with an average period of 14 weeks of immobilization. No patient experienced wound healing difficulty or disruption of a superficial nerve. The authors believe that this is a simple technique that permits excellent visualization through a safe internervous interval, good bone apposition, rigid interfragmentary fixation and does not require the use of bone graft.

Adult↗
PubMed1990

Murine interstitial nephritis. IX. Induction of the nephritogenic effector T cell repertoire with an antigen-specific T cell cytokine.

The experiments presented in this report describe the biochemical and functional characteristics of a soluble Th cell factor (ThF) which can induce a nephritogenic effector T cell repertoire producing autoimmune interstitial nephritis. The ThF is Ag-specific, I-A-restricted, and comprises two chains noncovalently linked as a heterodimer. One chain at approximately 78,000 Mr is related to the TCR/Id and expresses a framework determinant (14-30) common to Ag-binding factors, and the other chain at approximately 82,000 Mr is I-A+. Together these chains can replace their parent cell by providing cognate help to precursor effector T lymphocytes in the presence of accessory cells, tubular Ag, and IL-2.

Animals↗
PubMed1990

Hallux rigidus.

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Foot Deformities, Acquired↗