Multiple sclerosis and canine distemper on Key West, Florida.
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Biomedical subjects
Publications and source records attributed to S D Cook.
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A number of studies have demonstrated that high-dose corticosteroid treatment improves the rate of recovery from acute exacerbations of multiple sclerosis. The beneficial effect is more rapidly and consistently produced by high-dose corticosteroid administration than with adrenocorticotropic hormone. The most rapid improvement in clinical condition and cerebrospinal fluid parameters of patients has been observed with short courses of very high-dose intravenous therapy. This form of treatment would be most advantageous for patients with severe and rapidly progressive exacerbations. Ultimately, the duration of treatment will depend on the patient's response to treatment, tolerance of corticosteroid withdrawal, and the occurrence of significant complications of therapy. However, in our experience, a three- to four-month slowly tapered course of oral therapy is often needed, and is usually well tolerated, with few serious side effects when given once daily in the morning.
We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases.
A mechanical and histological evaluation of uncoated and hydroxylapatite-coated titanium implant materials was performed. Cylindrical implants of uncoated commercially pure (CP) titanium and hydroxylapatite-coated Ti-6Al-4V alloy were studied using a transcortical model, with implants evaluated after periods of 3, 5, 10, and 32 weeks. All implants had a surface macrotexture consisting of a series of semicircular annular grooves, approximately 750 micron in maximum depth. The attachment characteristics of interface shear stiffness and interface shear strength were determined by mechanical push-out testing. Nondecalcified histologic and microradiographic techniques, with implants in situ, were used to evaluate the response to the implant materials and the presence of the surface macrotexture. Mechanical testing results indicated that the hydroxylapatite-coated implants exhibited significantly greater values of maximum interface shear strength than the uncoated implants after all time periods. Interface shear stiffness was also significantly greater at all time periods for the hydroxylapatite-coated implants as compared to the uncoated implants. Histological evaluation after 3 weeks revealed an osteoid layer covering on all areas coated with the hydroxylapatite material; mineralization of this layer appeared to be complete after 10 weeks. In all cases, longer-term implants demonstrated mineralization of interface bone directly onto the hydroxylapatite coating, and in no case was a fibrous layer observed between the hydroxylapatite coating and the interface bone. Sections from the uncoated CP titanium implants revealed a thin fibrous layer present in nearly all areas. Only isolated regions of direct bone-implant apposition were observed for the uncoated implants. The presence of this fibrous tissue layer, however, apparently did not adversely affect the development of considerable attachment strength. The results from this study indicate that the hydroxylapatite coating can significantly increase the attachment strength of implants which rely upon bone apposition for fixation. In addition, the hydroxylapatite coating provides an osteophilic surface for bone deposition, and allows for a more rapid development of implant-bone attachment.
Primary organ cultures of rabbit corneal epithelium, stroma, and endothelium were established by microdissection. Secondary cultures of epithelial cells, keratocytes, and endothelial cells were established by serial passage. The doubling time for epithelial cells and keratocytes was 18 h, and endothelial cells doubled their number in 5 days. Ultrastructural studies demonstrated characteristic morphological, nuclear, and cytoplasmic features of corneal epithelial cells, keratocytes, and endothelial cells and confirmed the identity of the cell lines. The purity of the three distinct cell types was ascertained by indirect immunofluorescence techniques, using antibodies against keratin, which identified epithelial cells, and fibronectin, which identified keratocytes and endothelial cells. The indirect immunofluorescence technique represents a simple method to screen an aliquot of a cell suspension and determine the purity of corneal cells grown in vitro.
The in vivo performance of 250 retrieved internal fixation plates was evaluated. The corrosion characteristics and metallurgical properties of each implant were assessed and correlated with respective clinical performance. Screw-plate interface corrosion and screw surface corrosion were graded; Rockwell hardness, grain size, thin inclusion content, and heavy inclusion content measurements were made. The devices studied included 169 bone plates, 59 Richards type hip screw-plates and 22 Jewett type hip nail-plates. The devices remained in situ for an average of 26.3 months, with in situ periods ranging from 1 to 192 months. The majority of the plates (50.4%) were removed due to cause-related reasons, while the remaining devices (49.6%) were removed on a routine asymptomatic basis. The primary symptomatic removal reasons consisted of implant related pain, nonunion or malunion, infection, loosening and implant breakage. Upon stereomicroscopic examination, 89% of all plates exhibited some degree of interface crevice corrosion, and 88% of all screws exhibited some degree of surface corrosion. Statistical analysis of corrosion gradings and metallurgical data revealed significant correlations between the two. As was suggested in our previous study of a limited number of implants, this study demonstrates that stricter manufacturing standards for metallurgical properties would serve to enhance corrosion resistance and improve the in vivo performance of stainless steel internal fixation devices. It is also suggested that the routine removal of all internal fixation plates after fracture healing has been achieved would reduce the occurrence of symptomatic complications, such as implant breakage, implant loosening and implant related pain.
Herpes simplex virus type 1 (HSV-1) has been isolated from explanted human corneas after cultivation in vitro. To determine whether HSV-1 is persistent or latent in corneal cells, a system to study HSV-1 infection of rabbit corneal cells in vitro was developed. By elevation of the incubation temperature to 42 degrees C before and during HSV-1 infection it was shown that both keratocytes and epithelial cells support a nonproductive rather than a productive infection. On subsequent temperature reduction to 37 degrees C, infectious virus was released from both cell types. Addition of the viral inhibitor acycloguanosine during the last 5 days of a 14 day incubation at 42 degrees C did not reduce the frequency of viral shedding following transfer to 37 degrees C, indicating that corneal cells support a latent as opposed to persistent infection. Cultures which failed to shed virus spontaneously up to 29 days post-inoculation were superinfected at 37 degrees C, with an XbaI site deletion mutant of HSV-1. Restriction endonuclease analysis of progeny identified both the initial infecting virus and recombinants between the parental and superinfecting genomes.
Rabbits were inoculated in the left cornea with one of three strains of herpes simplex virus (HSV) i.e. HSV-1 strain 17, HSV-1 strain McKrae, HSV-2 strain HG52, or with and HSV-1 McKrae/HSV-2 HG52 recombinant R40/2. Fifty-nine to 67 days after inoculation trigeminal ganglia and corneas were explanted and screened for release of infectious virus. Virus was isolated from all left trigeminal ganglia after organ culture irrespective of viral strain. Virus was isolated from three of 16 corneas of animals inoculated with HSV-1 strain McKrae and from one of four corneas from animals inoculated with the HSV-1/HSV-2 recombinant. The isolation of HSV from explanted corneas, after between 15 and 35 days in organ culture suggests that the cornea may be a site additional to dorsal root ganglia where latent HSV can reside in rabbits.
Rhino-orbital-cerebral mucormycosis is an acute fungal infection of the oropharynx, paranasal sinuses, orbit and intracranial structures. It is rare, occurring mainly in diabetics in ketoacidosis. The clinical presentation is highly suggestive of the diagnosis. Current treatment has resulted in a greatly improved prognosis for survival and clinical awareness of this disease is important for early initiation of treatment with optimal effect. A clinico-pathological report of two cases is presented.
A retrospective study of endoprosthetic replacements and total hip prostheses was undertaken to determine factors that have the greatest effect on the success or failure of femoral hip components. A total of 227 endoprostheses were inserted within the years 1970-1985. Of these, 67 components (29.5 percent) required removal for various reasons. For an endoprosthesis, the most significant factor in determining the chances of success appeared to be the initial insertion diagnosis. Patients who received an endoprosthesis for an ailment which affected only the femoral side of the joint (such as traumatic fracture) had a much lower rate of failure than those patients with disease etiologies that could affect the acetabulum (such as osteoarthritis). The opposite was found for total hip prostheses. Of the 641 total hip devices inserted, 148 (23.0 percent) required removal. The highest rate of failure among these total hip components was for those devices inserted for trauma and the lowest rate of failure was for those inserted for osteoarthritis. Age at the time of insertion also proved to be of importance when estimating a hip component's chance of survival. For both endoprosthetic replacements and total hip arthroplasties, patients younger than 50 years of age at insertion experienced a failure rate almost twice that of those patients more than 50 years of age at insertion.
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A unicompartmental knee implant was retrieved after 11 years in situ. The cast stainless steel femoral component had fractured approximately 1 cm from the anterior tip. The implant and clinical tolerance were analyzed to ascertain the factors associated with the mechanical failure. Increased tensile stresses owing to poor surgical placement and wear on the weight-bearing surface of the component, together with the quality of implant material, influenced the mechanical failure. Examination of the fracture surface revealed fatigue to be the mode of failure. Microscopic analysis of sections through the specimens showed a high inclusion content and inhomogeneous grain size, typical of the cast stainless steel from which the femoral component was fabricated.
The interface shear properties of porous coated Ti-6Al-4V alloy embedded in bone cement were examined as a function of pore size. Cylindric Ti-6Al-4V alloy push-out specimens were coated with two layers of spheric powders having particle size ranges of 297-420 microns, 420-500 microns, 595-707 microns, and 850-1400 microns. Sintering resulted in mean pore sizes of 165, 285, 345, and 550 microns, respectively, and porosities in the range of 40%-44%. There was a statistically significant difference between the mean pore sizes obtained from the four particle size ranges. There were no differences between the mean porosities. The porous-coated specimens were embedded in bone cement and mechanical push-out testing was performed. Non-coated specimens having a satin surface finish were also embedded in bone cement and tested. The noncoated metal specimens displayed an interface shear strength of 4.2 +/- 0.4 MPa, whereas the shear strengths for the porous-coated specimens were significantly higher and increased as pore size increased. The mean interface shear strengths determined were 17.0 +/- 2.1 MPa (165 microns pore size), 18.1 +/- 2.3 MPa (285 micron pore size), 23.6 +/- 1.7 MPa (345 microns pore size), and 25.4 +/- 3.4 MPa (550 microns pore size). Significant differences in shear strength for the porous-coated specimens were found between the two smaller particle sizes and the two larger particle sizes. As pore size increased from 285 microns to 345 microns, a statistically significant increase in shear strength from 18.1 MPa to 23.6 MPa was observed.
Total lymphoid irradiation (TLI; 1980 cGy) or sham irradiation was given to 40 patients with chronic progressive multiple sclerosis (MS) in a prospective, randomised, double-blind study. During mean follow-up of 21 months, MS patients treated with TLI had less functional decline than sham-irradiated MS patients (p less than 0.01). A significant relation was noted between absolute blood lymphocyte counts in the first year after TLI and subsequent course, patients with higher lymphocyte counts generally having a worse prognosis (p less than 0.01). TLI was well tolerated and associated with only mild short-term, and to date, long-term side-effects.
We constructed a measles virus genomic recombinant DNA library, and used clones coding for portions of the viral P, M and H proteins to probe for measles virus nucleic acid sequences in post-mortem multiple sclerosis, SSPE and control brains. By dot blot hybridization, the probes detected measles virus nucleic acid sequences in as little as 3 nanograms of total RNA extracted from measles virus-infected cells and also in highly diluted RNA extracted from SSPE brain, but did not detect measles virus sequences in RNA extracted from 11 multiple sclerosis or 8 control brains, even at a 1 000-fold higher concentration of RNA. By in situ hybridization, these probes detected measles virus nucleic acid sequences in virtually every cell and the surrounding neuropile of SSPE brain, but again did not detect such sequences in multiple sclerosis or control brains. Our findings using these highly specific probes confirm that measles virus is found in SSPE brains and indicate that measles virus genome is unlikely to be present in multiple sclerosis or normal brains.
The efficacy of ceramic hydroxylapatite implant materials as graft materials for cervical spine fusion was evaluated in canines. Bioresorbable and non-bioresorbable systems were evaluated at time periods ranging from 1 to 24 weeks. Implant interbody position and progression of fusion were evaluated radiographically and histologically. Implant fracture and extrusion into adjacent soft tissues occurred in nine of 23 cases. Implant fracture occurred in many of the remaining 14 cases, however, the implant materials remained within the interspace. Implant fracture occurred with both implant systems. Radiographically little evidence of fusion was observed at less than 6 weeks, however by 12 weeks evidence of fusion was noted and was confirmed histologically. No difference in fusion rate or degree of fusion was observed between the two implant systems.