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Biomedical subjects

D R Sumner

Publications and source records attributed to D R Sumner.

84 records · Page 5Linked to original sources

Hemoglobin Windsor or beta 11 (A8)Val----Asp: a new unstable beta-chain hemoglobin variant producing a hemolytic anemia.

A new beta-chain variant, Hemoglobin Windsor [beta 11 (A8)Val----Asp] was discovered in a 9-month-old child who presented with a hemolytic anemia of 59 g/l with an intercurrent viral infection. Her blood film demonstrated fragmented cells, target cells, stipple cells, nucleated red cells, polychromasia and some spherocytes, indicative of acute hemolysis. Hemoglobin electrophoretic studies were requested and a beta-chain variant, constituting 27% of the total hemoglobin, separated towards the anode under alkaline conditions. The variant was unstable, producing numerous "Hb H"-like inclusions and a positive isopropanol stability test. The variant hemoglobin was purified by precipitation. The variant beta-chain was purified by column chromatography and its tryptic peptides fractionated by high performance liquid chromatography. Amino acid analysis and sequence data indicated that the valine at position 11(A8) had been substituted by an aspartic acid residue. This substitution, in the bottom of the heme pocket, has resulted in instability of the hemoglobin molecule and an increase in oxygen affinity. The variant appears to have resulted from a spontaneous mutation as both parents are hematologically normal. A younger sibling is also hematologically normal.

Amino Acid Sequence↗

Symmetry of the canine femur: implications for experimental sample size requirements.

The purpose of this study was to determine the degree of bilateral variability in cross-sectional geometric properties of the adult canine proximal femur and to use these data to determine minimum detectable treatment effects in paired and independent experimental designs. Thirteen pairs of canine femora were sectioned at nine locations and 16 cross-sectional geometric properties were determined for each section location. The canine femur was found to be bilaterally symmetrical. For a given sample size, the magnitude of the detectable treatment effect was (a) smaller for diameters than for areas and area moments of inertia and (b) smaller within the middiaphysis than proximally. The data from this study can be used to estimate sample size requirements for experiments in which the treatment effect is determined by using the contralateral femur as a control. It was found that an increase from 3 to 7 animals would have a much greater effect on improving the sensitivity of an experiment than would an increase from 7 to 11 animals.

Animals↗

Hemoglobin Randwick or beta 15 (A12)Trp----Gly: a new unstable beta-chain hemoglobin variant.

A new beta-chain hemoglobin variant, Hb Randwick [beta 15(A12)Trp----Gly] was detected in a 43-year-old female of Northern Italian parentage. During investigation for possible diabetes, mild red cell changes were noted and hemoglobin electrophoresis studies were requested. Independently, her sister's assessment had resulted in similar investigations. The most prominent findings were numerous "Hb H"-like inclusions and a positive isopropanol stability test. The hemoglobin variant separated poorly towards the anode at pH 9.2 and the level was estimated to be between 48-50% of the total hemoglobin. The variant beta-chain was partially purified by column chromatography, and its tryptic peptides fractionated by high performance liquid chromatography. Amino acid analysis and sequence data indicated that the tryptophan at residue 15 (A12) had been substituted by a glycine residue. Further study has indicated that eight other family members are heterozygous for the variant; they are clinically normal with no evidence of splenomegaly or history of jaundice, although four of them showed a mild reticulocytosis.

Adult↗

Hemoglobin Hobart or alpha 20(Bl)His----Arg: a new alpha chain hemoglobin variant.

A new alpha chain hemoglobin variant, Hb Hobart, alpha 20(Bl)His----Arg, was detected in a 60-year-old female of British nationality. The proposita had a history of severe rheumatoid arthritis and had been treated for many years for a refractory microcytic anemia and/or iron deficiency. A hemoglobin electrophoresis screen indicated the presence of a hemoglobin variant, with electrophoretic characteristics similar to a Hb Lepore. However, the level of the variant (17.9%) and the presence of a minor variant Hb A2 band (0.4%) suggested that further investigation was indicated. The variant hemoglobin was purified by column chromatography and the alpha chain subjected to aminoethylation and tryptic digestion. Peptide mapping and amino acid analysis indicated that the histidine residue 20 had been substituted by an arginine residue. The substitution in Hb Hobart is at the first residue in the B Helix of the alpha chain of hemoglobin. As this is an externally placed amino acid in the hemoglobin molecule, a substitution at this position of the hemoglobin molecule would not be expected to cause any functional problems. A family study has shown that at least three other relatives are heterozygous for Hb Hobart. These family members have normal hematological findings.

Amino Acids↗

[Surface structures and bone ingrowth in cement-free fixed prostheses].

Non-cemented implants are used primarily for hip and knee arthroplasties. Bone ingrowth into porous surfaces of different materials is required. Criteria of long-term success are primary stable fixation and the achievement of intimate bone contact by press-fit. However, animal experiments show that interdigitation with porous coating induces osteoporosis of the surrounding cortex. It appears that bony fixation gives rise to fewer problems in the acetabulum than in the femur. The results of animal experiments and follow-up studies in humans are used to compare potential problems of fixation without cement with the results obtained with bone cement.

Aged↗

A comparative study of porous coatings in a weight-bearing total hip-arthroplasty model.

The purposes of this study were to compare ingrowth of bone into three types of porous coating and to determine the effect of the type of porous coating and the degree of coverage of the stem on the remodeling of bone on the femoral side in cementless hip arthroplasty. A left total hip arthroplasty was performed in forty dogs. Thirty of the dogs had a titanium-alloy femoral prosthesis that had had one of three types of commercially pure titanium porous material applied along the length of the anterior and posterior surfaces of the stem: ten with sintered fiber-metal, ten with sintered beads, and ten with plasma flame-spray coating. The remaining ten dogs had a femoral component that was circumferentially coated with commercially pure titanium that was plasma flame-sprayed along the length of the stem. In each group, five animals were killed at one month and five were killed at six months. Ingrowth of bone into all three types of porous coating was observed, indicating secure fixation of all components. By six months, there was more ingrowth of bone and new medullary bone adjacent to the proximal and distal aspects of the stems compared with the middle level of the stems in all groups. No significant difference in ingrowth of bone was observed in the beaded surface (25.2 per cent) and the fiber-metal surface (16.6 per cent) at one month, but at six months there was significantly less ingrowth into the beaded surface (23.3 per cent) than into the fiber-metal surface (37.3 per cent). In all groups, a proximal-to-distal gradient of loss of cortical bone was observed by six months. The group of dogs that had the stem with the circumferential coating experienced more severe loss of bone than did the three groups that had a stem with a partial coating. The magnitude of loss of bone was dependent on the extent rather than the type of porous coating.

Animals↗

Computed tomography and automated image analysis of prehistoric femora.

Non-invasive characterization of limb bone cross-sectional geometry would be useful for biomechanical analyses of skeletal collections. Computed tomography (CT) is potentially the method of choice. Additionally, CT images are suitable for automated analysis. CT is here shown to be both accurate and precise in the analysis of cross-sectional geometry of prehistoric femora. Beam hardening artifacts can be reduced by using a water bath. As the availability of CT for research increases, both bone density and geometry could be determined simultaneously with this method.

Autoanalysis↗

Postembryonic dimensional allometry of the human femur.

Developmental constraints can affect evolution. McMahon 's (1973, 1975a ) hypothesis of elastic similarity is tested as an epigenetic rule. This is an ontogenetic hypothesis that previously has not been tested with ontogenetic data. Cross-sectional data from the human femur are analyzed. Length-diameter relationships for phases of growth and aging are calculated with bivariate allometry. McMahon 's hypothesis cannot be rejected, although most of the calculations are not consistent with it. Ontogenetic skeletal allometry is complex because both material and geometric properties change during development.

Adolescent↗

ESB Research Award 1992. The mechanism of bone remodeling and resorption around press-fitted THA stems.

A major problem threatening the long-term integrity of total hip replacement is the loss of proximal bone often found around noncemented stems in the long term. It is generally accepted that 'stress shielding' is the cause for this problem: after implantation of the prosthesis the surrounding bone is partially 'shielding' from load carrying and starts to resorb. One of the proposed answers to this problem is the application of press-fitted stems. These smooth-surfaced implants are thought to provoke higher proximal bone loading, and, hence, less stress shielding than bonded implants, because they are wedged into the femur every time when loaded. However, in a two-year experiment in dogs, similar amounts of resorption of the proximal cortex were found around press-fitted and bonded implants. The question arises how similar resorption patterns can develop under completely different stress conditions, and whether this phenomenon can be explained by adaptive bone remodeling theories based on Wolff's law. In the present study an answer was sought for this question. An advanced iterative computer simulation model was used to analyze the remodeling process in the animal experiment. Three-dimensional finite element models were constructed from the animal experimental configuration, in which smooth, press-fitted stems were applied unilaterally in the canine. The FE model was integrated with iterative remodeling procedures, validated in earlier studies. In the model an appropriate non-linear representation of the loose bone-implant interface was realized, also capable of simulating the proximal interface gap that was found around the uncoated implants. The simulation models predicted similar amounts of proximal bone loss and distal bone densification as found in the animal model. Hence, the cortical bone loss could indeed be predicted by the strain-adaptive bone remodeling theory. By unraveling the simulation process, the question stated above could be answered. Densification of the distal bone bed during the initial remodeling process was found to cause reduced axial stem displacement (elastic subsidence), decreasing the wedging effect of the stem and, hence, decreasing the loading of the proximal bone, resulting in proximal bone loss. Hence, whereas in the case of bonded stems the proximal resorption process develops monotonously to a new equilibrium, the process around smooth, press-fitted stems develops nonmonotonously. This is due primarily to the unbonded interface conditions and the development of a proximal fibrous membrane. The remodeling process then gradually causes the stem to be jammed in the distal diaphyses (proximal 'stress bypass').

Alloys↗

Relationship between articular cartilage damage and bone density in the first metatarsal.

It is well known that bone changes occur in relationship to the articular cartilage damage seen in osteoarthritis. Numerous studies have shown a relationship between bone density and articular cartilage damage in knee and hip joints, but it is controversial as to whether or not an increased subchondral bone density results in greater cartilage damage. We studied 49 pairs of cadaveric first metatarsals in an attempt to correlate the level of cartilage damage seen on the distal articular surface with areal and volumetric density and other parameters such as bone geometry. A positive correlation was detected between articular cartilage damage and bone density by peripheral quantitative computed tomography in five of eight frontal slices in the head of the left metatarsal in the male sample only. The more extensive subchondral cysts found in the right male metatarsal may have contributed to the lack of correlation between the two variables on the right side. In addition, females displayed significantly greater osteophytosis than males at a given grade of cartilage damage, thus, possibly leading to a painful, apropulsive gait and a disuse osteopenia which would neutralize any subchondral bone density increase associated with cartilage damage. Microscopic investigations are, therefore, warranted to detect bone changes on a more discreet level, particularly within the subchondral plate.

Adult↗

Bone remodeling in experimental total hip arthroplasty.

Experimental studies of cementless porous-coated total hip arthroplasty indicate that the most important design variable for femoral remodeling is stem stiffness. In the long-term (2 years) in the canine model, other variables including the presence, type and placement of the porous coating did not significantly affect the pattern of bone remodeling when tested with metallic stems. The basic pattern of bone remodeling was characterized by proximal cortical atrophy, and distal cortical and medullary bone hypertrophy. The use of low stiffness stems altered this pattern, leading to reduced proximal bone loss and no distal cortical hypertrophy.

Animals↗

[Histological study of the porous coating of the uncemented acetabulum. Apropos of 11 implants removed at autopsy].

Tissue ingrowth in the porous coating of 11 cementless acetabular components has been studied histologically. These cups were retrieved at autopsy from 8 patients who had undergone a primary total hip arthroplasty. Seven cups had a mean implantation period of 5.1 years, the other 4 had been in place for less than one year. This component was made of commercially pure (cp) titanium, with a porous surface of cp titanium fiber metal. The initial fixation of the cup was achieved by screws. The tissues of the porous coating were studied into 1 mm fields at four levels, and were categorized either as bone, marrow, cartilage or fibrous tissue. The fraction of void space within the porous coating occupied by bone was measured by backscattered scanning electron microscopy. The percentage of 1 mm fields with bony tissue was 20.9% and the fraction of void space occupied by bone was 12%. No regional significant difference was found. The number of fields with bone increased from the interface between the porous coating and the substrate of the cup to the interface between the outer surface of the porous coating and the host bone. All the screw threads were covered with lamellar bone. In the longest term cases, fine metallic and polyethylene debris were observed and their amount increased with time. This study showed that, despite the important variability in bone ingrowth, these cementless cups were able to give entire satisfaction to the patients.

Acetabulum↗