Corneal transplantation: how successful are we?
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Cornea↗
Biomedical subjects
S D Cook
Publications and source records attributed to S D Cook.
Cytokine secretion profile of myelin basic protein-specific T cells in multiple sclerosis.
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a presumed autoimmune pathogenesis involving autoantigen-specific CD4+ T cells and cytokines. A similar frequency of T cells responding to myelin basic protein (MBP), a putative target in MS, has been observed in MS patients and controls. To dissect the differences between MBP-specific T cells in patients and controls, we have analyzed the cytokine secretion profile of such autoreactive T cells. MBP-specific T cell clones (TCC) were isolated from the peripheral blood of MS patients and controls by limiting dilution. Expression of mRNA for interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-10, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) was assessed by polymerase chain reaction whereas secretion of cytokine protein was measured by ELISA. MBP-specific TCC exhibited a heterogeneous cytokine secretion profile with clones displaying Th1, Th2 and Th0 phenotypes. A significant difference in the distribution of the cytokine profile was noted between MS patients and controls. Although the frequency of Th1 secreting MBP-reactive TCC was similar between MS patients and controls, stable MS patients had a significant association with the Th0 phenotype whereas healthy individuals were associated with the Th2 phenotype. In comparison to control TCC, MBP-specific TCC from MS patients secreted increased amounts of IFN-gamma, IL-4 and IL-10 and decreased quantities of TGF-beta. Thus, these studies suggest that there is a dysregulation in the balance between pro-inflammatory Th1 and anti-inflammatory Th2 cytokines in MS. It appears that the presence of Th1 secreting autoreactive T cells in healthy individuals may be counterbalanced by the presence of cells secreting Th2 cytokines and by the augmented production of the immunosuppressive cytokine TGF-beta, whereas in MS there is a decrease in these anti-inflammatory agents.
Adult↗
Pride of the nation tomorrow. Where UMDNJ is headed.
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Education, Medical, Undergraduate↗
Early changes in nutrient artery blood flow following tibial nailing with and without reaming: a preliminary study.
OBJECTIVE: To quantify the changes in nutrient artery blood flow following reamed and unreamed nailing of intact canine tibias. DESIGN: In vivo animal study. INTERVENTION: Eighteen dogs underwent nutrient artery blood flow measurements over a fourteen-day period. The intervention groups consisted of controls (Group I), nailing without reaming (Group II), and nailing with reaming (Group III). MAIN OUTCOME MEASUREMENTS: Nutrient artery blood flow was measured through implantable ultrasonic blood flow probes placed around the nutrient artery of the tibia. RESULTS: Nutrient artery blood flow averaged 1.94 milliliters per minute over the fourteen-day period in Group I (no reaming or nailing performed). Nutrient artery blood flow following nailing without reaming (Group II) decreased to 44 percent of baseline values immediately after the procedure. By postoperative day 1, flow had decreased to 23 percent of baseline; over the fourteen-day period, nutrient artery blood flow recovered toward baseline values. Immediately following nailing with reaming (Group III), nutrient artery blood flow measured zero milliliters per minute. Over the fourteen-day period, nutrient artery blood flow in this group averaged 39 percent of the baseline level (range 19 to 58 percent). Whereas nutrient artery blood flow recovered toward baseline values (99 percent of baseline) by fourteen days in Group II, nutrient artery blood flow measured only 26 percent of the baseline level on postoperative day fourteen in Group III. CONCLUSIONS: The preliminary data suggest that nailing with reaming provides a double insult to the nutrient artery distribution.
Animals↗
Correlation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis.
OBJECTIVE: To determine if sex hormones play a role in the pathogenesis of multiple sclerosis (MS) by correlating serum estradiol and progesterone levels with gadolinium (Gd) enhancing lesions on magnetic resonance imaging (MRI) in MS. METHODS: Thirty patients with MS were studied with Gd enhanced brain MRI and simultaneous serum estradiol and progesterone levels either during the early follicular, late follicular or luteal phases of their menstrual cycle. Correlation between hormone levels and number of Gd enhancing lesions was determined. RESULTS: Patients with high estradiol and low progesterone levels had a significantly greater number of Gd enhancing lesions than those with low levels of both these hormones. Patients with a high estrogen to progesterone ratio had a significantly greater number of active MRI lesions than those with a low ratio. CONCLUSION: Estradiol and progesterone may influence disease activity in MS. If further studies confirm these results, it may be possible to develop therapy by altering levels of these hormones.
Adult↗
Proposed classification for topographic patterns seen after penetrating keratoplasty.
AIMS: To create a clinically useful classification for post-keratoplasty corneas based on corneal topography. METHODS: A total of 360 topographic maps obtained with the TMS-1, from 95 eyes that had undergone penetrating keratoplasty (PKP), were reviewed independently by two examiners in a masked fashion, and were categorised according to a proposed classification scheme. RESULTS: A high interobserver agreement (88% in the first categorisation) was achieved. At 12 months post-PKP, a regular astigmatic pattern was observed in 20/85 cases (24%). This was subclassified as oval in three cases (4%), oblate symmetric bow tie in six cases (7%), prolate asymmetric bow tie in six cases (7%), and oblate asymmetric bow tie in five cases (6%). An irregular astigmatic pattern was observed in 61/85 cases (72%), subclassified as prolate irregular in five cases (6%), oblate irregular in four cases (5%), mixed in seven cases (8%), steep/flat in 11 cases (13%), localised steepness in 16 cases (19%), and triple pattern in three cases (4%). Regular astigmatic patterns were associated with significantly higher astigmatism measurements. The surface asymmetry index was significantly lower in the regular astigmatic patterns. CONCLUSIONS: In post-PKP corneas, the prevalence of irregular astigmatism is about double that of regular astigmatism, with a trend for increase of the irregular patterns over time.
Astigmatism↗
Impaired interleukin-12 production in multiple sclerosis patients.
Multiple Sclerosis (MS), a disease of the human central nervous system, is believed to be a T cell mediated autoimmune disorder with genetic and environmental influences. Interleukin-12 (IL-12), a proinflammatory cytokine produced primarily by antigen presenting cells is a potent inducer of interferon-gamma (IFN-gamma) and other Th1 cytokines that may play an important role in MS pathogenesis. We have investigated IL-12 production induced by the T cell independent pathway in untreated and IFN-beta treated MS patients, healthy individuals and other neurological disease (OND) patients in response to the human pathogen Staphylococcus aureus. We report that peripheral blood mononuclear cells (PBMC) from untreated MS patients produce normal amounts of the biologically active IL-12 p70 heterodimer but significantly less free IL-12 p40 heavy chain than PBMC from both healthy and disease controls when challenged in vitro with Staphylococcus aureus. Both mRNA expression of the inducible IL-12 p40 chain and protein levels were found to be reduced in untreated MS patients. No decrease in the production of the IL-12 p40 was seen in MS patients on IFN-beta therapy. The decreased production of IL-12 p40 heavy chain is not attributed to increased IL-10 secretion, a defect in the production of cytokines by macrophages or the number of cytokine producing cells. The factor(s) responsible for the decrease in p40 remain to be determined. Since IL-12 p40 antagonizes the biological activity of IL-12 in vitro and in vivo, identification of a defect in the 'natural' antagonist of IL-12, may provide the basis for immune therapy.
Adolescent↗
Long-term follow-up of pyrolytic carbon metacarpophalangeal implants.
BACKGROUND: The metacarpophalangeal joint is the most commonly involved joint when rheumatoid arthritis affects the hand. Many prosthetic implants have been designed for the replacement of this joint. Although studies of these implants have shown relief of pain, they have generally demonstrated a poor range of motion, progression of ulnar drift, and bone loss, as well as failure, fracture, and dislocation of the implant. METHODS: From December 1979 to February 1987, 151 pyrolytic carbon metacarpophalangeal implants were inserted in fifty-three patients. The implants had an articulating, unconstrained design with a hemispherical head and grooved, offset stems. Forty-four patients had rheumatoid arthritis; five, posttraumatic arthritis; three, osteoarthritis; and one, systemic lupus erythematosus. Three patients (eleven implants) were lost to long-term follow-up, and twenty patients (fifty-one functioning implants) died after the implant had been in situ for an average of 7.2 years. Eighteen implants (12 percent) in eleven patients were revised. Fourteen of the eighteen implants were replaced with a silicone-elastomer or another type of implant, and the remaining four were removed and a pyrolytic carbon implant was reinserted with the addition of bone cement or bone graft, or both. Twenty-six patients (seventy-one implants) were available for long-term review at an average of 11.7 years (range, 10.1 to 16.0 years) after implantation. RESULTS: The implants improved the arc of motion of the fingers by an average of 13 degrees and elevated the arc by an average of 16 degrees. As a result, fingers were in a more functional, extended position. A complete set of preoperative, postoperative, and follow-up radiographs was available for fifty-three of the seventy-one implants that were followed long term. There was a high prevalence of joint stability: fifty (94 percent) of the fifty-three implants were in a reduced position postoperatively, and forty-one (82 percent) of those fifty implants were still in the postoperative reduced position at the time of long-term follow-up. Ulnar deviation averaged 20 degrees preoperatively and 19 degrees at the time of follow-up, with only the long finger having an increase in deviation. No adverse remodeling or resorption of bone was seen. Fifty (94 percent) of the fifty-three implants had evidence of osseointegration, with sclerosis around the end and shaft of the prosthetic stems. Radiolucent changes were seen adjacent to twelve implants. There was minimum-to-moderate subsidence (four millimeters or less) of thirty-four implants; most of the subsidence occurred immediately postoperatively. Survivorship analysis demonstrated an average annual failure rate of 2.1 percent and a sixteen-year survival rate of 70.3 percent. The five and ten-year survival rates were 82.3 percent (95 percent confidence interval, 74.6 to 88.2 percent) and 81.4 percent (95 percent confidence interval, 73.0 to 87.8 percent), respectively. None of the revised implants had any visible changes of wear or deformity of the surfaces or stems. Four instances of chronic inflammatory tissue and three instances of proliferative synovitis were noted histologically. Focal pigment deposits were seen in three fingers, one of which had removal of the implant two months after a fracture. No evidence of intracellular particles or particulate synovitis was found. CONCLUSIONS: The results of this study demonstrate that pyrolytic carbon is a biologically and biomechanically compatible, wear-resistant, and durable material for arthroplasty of the metacarpophalangeal joint.
Arthritis, Rheumatoid↗
Preclinical and clinical evaluation of osteogenic protein-1 (BMP-7) in bony sites.
Osteogenic proteins (OPs), also referred to as bone morphogenetic proteins (BMPs), are a family of bone-matrix polypeptides isolated from a variety of mammalian species. Implantation of osteogenic proteins induces a sequence of cellular events that leads to the formation of new bone. In preclinical studies, the implantation of recombinantly produced human osteogenic protein-1 (OP-1, also referred to as BMP-7) into surgically created, critical-size diaphyseal segmental defects resulted in the regeneration of new bone that was fully functional biologically and biomechanically. Injection of an OP-1 solution into a fresh fracture model accelerated the bone repair process compared with control fracture healing. This was the result of greater and earlier new bone formation. Further study has demonstrated that OP-1 can be used as a bone graft substitute to promote spinal fusion, aid in the incorporation of metal implants, and improve the performance of autograft and allograft bone. Clinical study of OP-1 implanted in conjunction with a bovine bone-derived type 1 collagen carrier for the treatment of tibial nonunion fractures has shown healing characteristics similar to that obtained with autogenous iliac crest bone graft. Advantages of OP-1 included no donor site complications, less blood loss, and a shorter operative time.
Animals↗
Stuart D. Cook, MD. President, UMDNJ.
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Ethics, Medical↗
Antibodies to GT1a ganglioside in patients with Guillain-Barré syndrome.
Serum antibodies from 8 (13%) of 62 patients with the acute Guillain-Barré syndrome (GBS) and 1 of 3 patients with the Miller Fisher syndrome (MFS) recognized a minor ganglioside in bovine and human brain trisialoganglioside fractions. The ganglioside antigen migrated between GD1a and GD1b on thin-layer chromatograms. The structure of this ganglioside was established to be GT1a by thin-layer chromatography blotting and mass spectrometry. GT1a a ganglioside was also detected in human and bovine peripheral nerves by thin-layer chromatogram immunostaining. Serum from the GBS patients had IgM, IgG, or IgA antibodies against GT1a detectable by enzyme-linked immunosorbent assay (ELISA). Serum from the MFS patient also had elevated levels of IG against GT1a. None of the sera from 43 patients with other neurological diseases or from 24 healthy controls reacted with GT1a. Sera from 6 of 8 GBS patients with anti-Gt1a antibodies also reacted with GQ1b. There was no difference in the incidence of anti-GT1a immunoglobulins in acute GBS patients with or without oculomotor abnormalities. Levels of anti-GT1a antibodies correlated temporally wit clinical symptoms in GBS patients. Although the incidence of dysphagia was slightly higher in GBS patients with anti-GT1a antibodies than in those without, the number of patients studied may have been too small to detect an association between anti-GT1a antibodies and an a specific clinical variant of GBS. Our data demonstrate that a proportion of GBS patients have antibodies against GT1a ganglioside and suggest that these antibodies may play a role in the pathogenesis of neuropathy in GBS.
Adult↗
Multiple sclerosis.
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History, 18th Century↗
Combined interrupted and continuous versus single continuous adjustable suturing in penetrating keratoplasty: a prospective, randomized study of induced astigmatism during the first postoperative year.
OBJECTIVE: To compare postoperative astigmatism induced by two different suturing techniques in penetrating keratoplasty (PKP). DESIGN: A monocenter, prospective, randomized clinical trial with a longitudinal 1-year follow-up. PARTICIPANTS: A total of 95 eyes undergoing PKP were randomized into 2 groups. Of these, 51 eyes were allocated to the combined interrupted and continuous suturing group (ICS) and 44 eyes to the single continuous adjustable suturing (SCAS) group. INTERVENTION: In the ICS group, suturing was with a combination of 12 interrupted 10-0 nylon and 1 continuous 11-0 nylon sutures. Eyes in the SCAS group had been sutured with a single running 24-bite 10-0 nylon. Selective suture removal started no earlier than 10 weeks after surgery; suture adjustment could start as soon as possible after surgery. MAIN OUTCOME MEASURES: Astigmatism was measured by topography, keratometry, and refraction at 3-, 6-, 9-, and 12-month postoperative intervals. RESULTS: The difference in mean time of suture manipulation between groups was significant (P = 0.0001), with the SCAS starting earlier. A significant decrease in astigmatism occurred by either interrupted suture removal (6.69 +/- 3.11 diopter [D] before to 4.76 +/- 2.99 D after, P = 0.0002) or suture adjustment (7.18 +/- 3.12 D before to 4.46 +/- 3.24 D after, P = 0.0001). However, the net astigmatic reduction in the SCAS group was not significantly greater (P = 0.250) than in the ICS group. Vector change was 7.40 +/- 4.17 D and 6.28 +/- 4.14 D for SCAS and ICS, respectively (P = 0.13). At no interval (3, 6, 9, or 12 months) was there significant difference in astigmatism between the two groups. Refractive astigmatism (cyl, D) at 1 year was 2.66 +/- 1.70 for the ICS and 3.12 +/- 2.62 for the SCAS, but there was no significant treatment effect (P = 0.945). Furthermore, 66% of the ICS eyes and 58% of the SCAS eyes (P = 0.295) were within the astigmatic target of the study (<3.5 D). CONCLUSIONS: Postkeratoplasty astigmatism can be decreased similarly with either adjustment of a single running suture or selective removal of interrupted sutures. No advantage of the SCAS over ICS in terms of fewer manipulations or less astigmatism was seen as suggested previously.
Adult↗
Surgical control of late postkeratoplasty astigmatism with or without the use of computerized video keratography: a prospective, randomized study.
OBJECTIVE: To assess the effectiveness of computerized videokeratography (CVK) in refining the surgical design and in improving predictability of surgical correction of postkeratoplasty astigmatism. DESIGN: A prospective, controlled, randomized, clinical trial. PARTICIPANTS: A total of 31 postkeratoplasty eyes, divided into 2 groups (group A, 16 eyes; group B, 15 eyes), with more than 4 diopters (D) of disabling astigmatism were studied. INTERVENTION: All eyes were treated with a combination of arcuate relaxing incisions and compression sutures. The surgical plan in group A was based on topographic information, whereas in the control group B, the surgical plan was based on information obtained by refraction and keratometry alone. MAIN OUTCOME MEASURES: Change in the surgical plan induced by the CVK information, astigmatism, topographic patterns, and factors associated with outcome were measured. RESULTS: In all 16 cases of group A, the use of CVK changed some aspect of the surgical plan. At 12 months after surgery, both groups showed a significant net reduction (P = 0.001) of baseline astigmatism. However, the reduction (47% and 41 % for groups A and B, respectively) did not differ significantly between the two groups. The topographic astigmatism at 12 months measured 4.24 +/- 0.71 D in group A and 5.60 +/- 0.51 D in group B (P = 0.139). Significant differences between the two groups at 12 months were seen only for keratometric astigmatism (3.60 +/- 0.81 D in group A vs. 5.77 +/- 0.52 D in group B, P = 0.035) and refractive astigmatism (2.34 +/- 0.37 D in group A vs. 4.88 +/- 0.52 D in group B, P = 0.000). The mean vector surgical effect was 91 % for group A and 70% for group B. Regular astigmatism patterns had a greater benefit from surgery than irregular patterns (P = 0.008). Previous refractive surgery was associated with less-favorable outcome (P = 0.045). CONCLUSIONS: The current study indicates that the use of CVK provides a benefit compared to keratometry and refraction alone in the planning and outcome of surgical treatment for high postgraft astigmatism.
Adolescent↗
Use of an osteoinductive biomaterial (rhOP-1) in healing large segmental bone defects.
OBJECTIVE: To assess the radiographic, histologic, and mechanical characteristics of new bone formation in large segmental bone defects treated with a new osteoconductive material, recombinant human osteogenic protein-1 (rhOP-1). DESIGN: In vivo animal study. INTERVENTION: Sixteen dogs (thirty-two limbs) with an ulna segmental defect (2.5 centimeters) were randomized to three treatment groups: rhOP-1, collagen alone, and no implant. MAIN OUTCOME MEASUREMENTS: Radiographic evidence of defect healing, mechanical testing (torsional strength) as compared with thirty-one control intact dog ulnas, and histologic analysis. RESULTS: At twelve weeks, complete radiographic healing was observed in twenty-five of twenty-eight defects (89 percent) treated with rhOP-1. The mechanical strength of the rhOP-1-treated defects at twelve weeks was 65 percent of that of intact ulnas. Histologic analysis revealed that defects treated with rhOP-1 were bridged with lamellar and woven bone that was in continuity with the host bone. CONCLUSIONS: The results indicate that osteoinductive materials, which have the ability to quickly fill and heal large defects, may have advantages over osteoconductive materials, which are typically used to fill smaller non-load-bearing bone voids.
Animals↗
Clinical evaluation of keratometry and computerised videokeratography: intraobserver and interobserver variability on normal and astigmatic corneas.
AIMS: To evaluate intra- and interobserver variability in measurements on normal and astigmatic corneas with keratometry and computerized videokeratography. METHODS: Keratometric readings with the 10 SL/O Zeiss keratometer and topographic maps with the TMS-1 were obtained by two independent examiners on 32 normal and 33 postkeratoplasty corneas. Inter- and intraobserver coefficients of variability (COR) for measurements of steep and flat meridian power and location, in addition to the magnitude of astigmatism, were assessed. RESULTS: Compared with TMS-1, the 10 SL/O keratometer showed a superior repeatability in measuring normal corneas (intraobserver COR for keratometry and TMS-1 respectively: 0.22 and 0.30 D for steep meridian power; 0.18 and 0.44 D for flat meridian power; 0.26 and 0.40 D for astigmatism; 5 degrees and 26 degrees for steep meridian location; 5 degrees and 13 degrees for flat meridian location). Astigmatism intraobserver COR (0.20 D and 0.26 D for the two observers) and interobserver COR (0.28 D) of the keratometer for normal corneas was very good and not affected by observers' experience. Repeatability of the TMS-1 on normal corneas was found to be: (a) observer related, and (b) astigmatism related. A novice observer showed a much greater COR (1.62 D for astigmatism, 30 degrees for flat meridian location) compared with the experienced examiner (0.40 D for astigmatism, 13 degrees for flat meridian location). Higher deviation scores were observed for corneas with higher astigmatism. For the postkeratoplasty corneas, again the keratometer achieved superior reproducibility (astigmatism interobserver COR 1.12 D for keratometry, 4.06 D for TMS-1; steep meridian location interobserver COR 10 degrees for keratometry, 34 degrees for TMS-1). CONCLUSION: Keratometric readings are more reproducible than topographic data both for normal and postkeratoplasty corneas. The two instruments should not be used interchangeably especially on highly astigmatic corneas. For the TMS-1, users with the same level of experience should be employed in clinical or experimental studies.
Adult↗
Free light chains in multiple sclerosis urine.
We measured free kappa (kappa) and lambda (lambda) light chains in urine from patients with definite multiple sclerosis (MS), other neurologic diseases (OND), and normal controls by using an enzyme linked immunosorbent assay. Both kappa and lambda light chains were higher in MS than OND or controls. In seven of eight relapsing-remitting (R-R) MS patients serial studies showed that urinary kappa chains were elevated during periods of worsening, and decreased during clinical recovery. In contrast, the levels of kappa chains did not correlate with clinical activity in 10 progressive (P) MS patients. Further correlation of urinary light chains with neurologic evaluations in R-R and P MS patients over a longer period are needed to determine their clinical and biological relevance.
Biomarkers↗
Airway dynamics, oesophageal pressure and cough.
This study hypothesizes that: peak supramaximal airflow during cough reflects expiratory muscle effort, and that expiratory muscle function during cough might be assessed from the airflow signal alone. We monitored airflow and oesophageal pressure (Poes) in normal subjects during cough generated under two conditions: 1) voluntarily from functional residual capacity (FRC); and 2) involuntarily after inhalation of citric acid (CA). Maximal expiratory cough flow was quantified as the quotient of maximal flow during a given cough divided by maximal flow at the matched volume of thoracic gas (Vtg) as identified on the maximal expiratory flow-volume curve. We found: flow ratios correlated poorly with Poes; the variance of flow ratios associated with a series of voluntary coughs was poorly explained by Poes. During CA inhalation, when the Vtg compressed during cough could not be controlled, correlation of Poes with flow ratio remained poor. We conclude that to study the motor limb of the cough reflex, measurements of both airflow and oesophageal pressure are required.
Administration, Inhalation↗