The effect of oral contraceptives on lumbar bone density in premenopausal women.
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Biomedical subjects
Publications and source records attributed to S D Cook.
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To determine whether immunosuppression by total lymphoid irradiation (TLI) slowed deterioration of chronic progressive multiple sclerosis (MS), functional impairment score and blood lymphocyte counts were compared at 6-month intervals through 4 years following treatment of MS patients by either TLI (n = 27) or sham irradiation (n = 21). At each interval, 20 to 30% fewer TLI-treated patients had deteriorated (p less than 0.05 at 6, 12, and 18 months), and the difference in mean functional impairment score between groups became progressively greater (p less than 0.01 at 42 and 48 months). Benefit accrued principally to the 17 TLI-treated patients with absolute blood lymphocyte counts less than 900/mm3 3 months after treatment, whose mean functional impairment score remained within 0.6 units of baseline (p = NS), whereas the ten TLI patients with higher post-treatment lymphocyte counts had progressive deterioration (p less than 0.05 to p less than 0.001 versus TLI-treated patients with lower lymphocyte counts at all intervals except 30 months) and had deteriorated by more than 5 functional scale units by 42 and 48 months. Side effects were minor and complications rare in TLI-treated patients, but one TLI-treated patient developed staphylococcal sepsis. Thus, TLI slows deterioration of chronic progressive MS, with what appears to be enduring benefit through 4 years compartmented to patients with greater induced lymphopenia. Modification of lymphoid irradiation regimens to increase the proportion of MS patients who achieve a favorable degree of lymphopenia and to avert functional hyposplenism may further improve the benefit/risk ratio.
The clinical and metallurgical performance of 12 retrieved Noiles total knee prostheses was investigated. Clinical histories and serial roentgenograms were used in conjunction with the American Society for Testing and Materials (ASTM) standard implant retrieval and analysis techniques to assess device performance. All of the devices were removed because of implant loosening with pain, while two devices also had a late infection. The average time in situ for all devices was four years. Roentgenographically, all of the devices showed signs of progressive radiolucencies. Ten (83%) of the devices migrated proximally within the femur. A marked varus drift was observed in eight (67%) of the retrieved prostheses. Hypertrophy of the femoral cortex was observed in eight (67%) of the cases. Seventy-three percent of the polyethylene tibial stems exhibited extensive wear on the anterior and medial aspects of the articulating surface. Extensive wear was also seen on the anterior and extreme posterior aspects in 92% of the polyethylene tibial plateau bearings. This wear was a consequence of the migration of the femoral component leading to buttressing of the plastic components against bone or bone cement. This study indicates serious design flaws in the Noiles knee prosthesis that unless corrected would question the use of the device in either primary or revision knee surgery.
A histologic and microradiographic analysis was performed on 90 retrieved human noncemented porous-coated total joint implants recovered from 58 patients. The specimens included 62 total knee components from 34 patients and 28 total hip components from 24 patients. All components were inserted without the use of bone cement, and in no case was the retrieved component removed due to clinically or roentgenographically apparent loosening. Approximately 92% of the total knee components and 93% of the total hip components had been in situ at least six weeks; 70% of the knee components and more than 50% of the hip components had been functional for at least nine months. The histologic sections and microradiographs revealed varying amounts of bone growth into or in apposition to the porous coatings. In approximately one third of the components, no bone ingrowth or apposition was observed. No component had greater than 10% of the available porous material ingrown with bone. No relationship between the degree of bone ingrowth and the length of time in situ was noted. In all components, the majority of the porous coating contained fibrous tissue that in some cases displayed orientation indicating evidence of load transmission capability. The adherence of bony tissue at the time of removal, a positive roentgenographic evaluation, or a positive clinical presentation was not found to be a definite prognosticator of bone ingrowth. It appears that the combination of limited bone ingrowth and extensive fibrous tissue ingrowth is adequate for implant fixation.
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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.