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Biomedical subjects

R McCabe

Publications and source records attributed to R McCabe.

At least 19 recordsLinked to original sources

Anterior cervical discectomy and fusion. A comparison of techniques in an animal model.

An animal model for three-level anterior cervical discectomy and fusion was established in the goat. Twenty-one goats underwent surgery, with seven goats in each of three experimental groups. In Group I, all seven goats underwent three-level anterior cervical discectomy without fusion. In Group II, each of the seven goats had a three-level discectomy with autogenous bone performed according to the Smith-Robinson technique. In Group III, fresh-frozen allograft bone was used for each of the three-level discectomy and fusion. Each goat was then killed after 12 weeks. Analysis consisted of radiographic review, fluorochrome labeling, biomechanical rigidity and flexion and extension, axial compressive load, and torsion. Histologic analysis was also performed for evidence of fusion and vertebral body histomorphometric analysis. The analysis of results showed that radiographic union was judged to have occurred in 0 of 21 Group I disc spaces, 10 of 21 Group II disc spaces, and 8 of 21 Group III disc spaces. Histologic fusion was judged to have occurred in 0 of 21 Group I goats, 10 of 21 Group II goats, and 0 of 21 Group III goats. The histologic fusion rate was significantly higher in Group II than either Group I or Group III. Biomechanically, the spines that had autogenous bone grafting (Group II) were significantly stiffer in compressive axial load and in extension. Both Group II and Group III were stiffer in flexion than Group I. An evaluation of the peri-endplate vascularity showed that the vascularity measured 10.4% in Group I, 16.7% in Group II, and 8.5% in Group III.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The relationship between environmental temperature, metabolic rate, sleep state, and evaporative water loss in infants from birth to three months.

We have investigated the effect of changing environmental temperature on metabolic rate, sleep state, and water loss in a longitudinal study of 22 lightly clothed babies from 2 d to 3 mo of age. Studies were performed in a modified barometric plethysmograph while recording sleep state, oxygen consumption, and skin and axillary temperatures. Oxygen consumption was higher in rapid eye movement sleep than in quiet sleep at all ages and varied widely between infants at each temperature. Within the first week, there was a 19% rise in oxygen consumption on cooling to 19-22 degrees C during rapid eye movement sleep and a 6% rise during quiet sleep. The median duration of quiet sleep periods was reduced from 17 to 12 min on cooling within the first week. No such change was seen at 1, 2, and 3 mo. Axillary temperature was reduced at 3 mo during cooling. This may be a part of normal patterns of change in temperature during sleep, unrelated to cooling. At each age, total evaporative water loss fell linearly with falling environmental temperature both within and below the temperature range at which metabolic rate was minimal. The evaporative water losses were greater than expected and suggested that sweating was occurring, both at temperatures at which metabolic rate was minimal and at those at which it was increased. The metabolic response to cooling and the process of sweating appear to be in dynamic equilibrium across this temperature range. Thus, it was not possible to define a temperature range over which both metabolic rate and evaporative water loss were at minimum values.

Body Temperature Regulation

Candida albicans purulent pericarditis treated successfully without surgical drainage.

Cures of Candida pericarditis reported in the literature uniformly involved surgical drainage of the pericardial space. We report a patient with purulent pericarditis caused by Candida albicans who was treated successfully with antifungal chemotherapy combined with a single pericardiocentesis that did not completely evacuate the pericardial space. This case indicates that thoracotomy with surgical drainage of the pericardium is not mandatory for successful therapy of Candida pericarditis.

Amphotericin B

Cervical stability after foraminotomy. A biomechanical in vitro analysis.

Laminectomy or facetectomy of the cervical spine, or both, may be needed for decompression of the spinal cord or of the nerve-roots. Acute stability of the cervical spine was tested after laminectomy and progressive staged foraminotomies in an in vitro model. Twelve cervical spines from human cadavera were used in the experiment. Biomechanical testing included the application of an axial load, the application of a flexion and extension moment, and the application of a torsional moment. Each specimen was tested intact, after laminectomy of the fifth cervical vertebra, and after progressive foraminotomy of the sixth cervical root. Foraminotomy was performed by resection of 25, 50, 75, and 100 per cent of the facet joint and capsule. Torsional stiffness decreased dramatically when more than 50 per cent of the facet had been resected. Statistically equivalent subsets were the intact specimen, laminectomy, 25 per cent facetectomy, and 50 per cent facetectomy in one subset, and 75 and 100 per cent facetectomy in the least-stiff subset. Flexion-moment testing showed that the posterior strain did not differ among three groups: the intact specimens, those that had been treated with laminectomy, and those that had been treated with a 25 per cent facetectomy. The 50 per cent facetectomy resulted in a 2.5 per cent increase in posterior strain, and the 75 or 100 per cent facetectomy, in a 25 per cent increase in posterior strain compared with the intact specimen. Segmental hypermobility of the cervical spine results if a foraminotomy involves resection of more than 50 per cent of the facet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

A randomized trial of cefepime (BMY-28142) and ceftazidime for the treatment of pneumonia.

Cefepime is a new cephalosporin with a broad antimicrobial spectrum that includes Staphylococcus aureus and Pseudomonas aeruginosa. To study the efficacy and safety of cefepime for treatment of pneumonia, 65 patients were randomized to therapy with either cefepime or ceftazidime at a two to one ratio. Of the 57 evaluable patients, 89% of the cefepime patients and 84% of the ceftazidime patients were cured clinically or improved. Haemophilus spp., Streptococcus pneumoniae, and Neisseria spp. were common pathogens. Bacteriological cure was achieved in 31 (91%) of cefepime patients and 17 (100%) ceftazidime patients. Adverse clinical and laboratory reactions possibly due to study drug occurred in 9 (21%) cefepime patients and in 1 (5%) ceftazidime patient. Most reactions were mild and resolved with discontinuation of study drug. In this study, cefepime appeared as effective as ceftazidime for the treatment of pneumonia.

Adult

Soluble HLA antigens, anti-HLA antibodies, and antiidiotypic antibodies in the circulation of renal transplant recipients.

Chronic rejection represents the major threat to long-term survival of organ allografts. It is presumed that this form of rejection is mediated by antibodies against mismatched HLA antigens of the graft. The presence and specificity of anti-HLA-antibodies in posttransplantation sera are, however, difficult to document. We have explored the possibility that anti-HLA antibodies form immune complexes with soluble HLA antigens released from the injured graft and/or that they are blocked by antiidiotypic, anti-anti-HLA-antibodies. Our data demonstrate that the long-term survival of renal allografts is significantly lower in patients who develop anti-HLA-antibodies following transplantation than in patients who do not form antibodies. Following depletion of soluble HLA antigens by magnetic immunoaffinity, we could identify anti-HLA-antibodies in 57% of the sera obtained from patients undergoing chronic rejection of kidney allografts, compared with 41% prior to antigen depletion. In patients tolerating the graft for 4 years or more, the corresponding frequencies of antibody-positive sera was 2% and 5% prior and following depletion of HLA antigens. The presence of HLA antigen/anti-HLA-antibody immune complexes in patients' sera was positively associated with chronic humoral rejection (P less than 0.0001). Patients who tolerated the graft in spite of having developed antibodies against one of its mismatched HLA antigens show specific antiidiotypic (anti-anti-HLA-antibodies). Such antiidiotypic antibodies were not found in sera from patients with chronic rejection (P = 0.005). This indicates that antiidiotypic antibodies may delay the progression of chronic humoral rejection.

Antibodies, Anti-Idiotypic

Gamma interferon suppresses acute and chronic Trypanosoma cruzi infection in cyclosporin-treated mice.

To determine if exogenous gamma interferon is effective in immunosuppressed mice infected with Trypanosoma cruzi, recombinant murine gamma interferon was administered to cyclosporin-treated mice with either acute or chronic T. cruzi infection. Gamma interferon significantly decreased parasitemia and prevented death in acutely infected mice. Parasitemias and mortality of mice treated with both gamma interferon and cyclosporin were similar to those of immunocompetent controls. In chronically infected mice, cyclosporin treatment produced significantly more organ explant cultures positive for T. cruzi. Fewer positive cultures, particularly for spleen and heart, were obtained from cyclosporin-treated mice when they also received gamma interferon. Ketoconazole treatment of mice resulted in no positive cultures. Cyclosporin treatment did not prevent activation of peritoneal macrophages by parenteral gamma interferon, nor did it have a consistent effect on serum titers of alpha/beta or gamma interferon in response to a second challenge inoculum of T. cruzi. These data indicate that exogenous gamma interferon suppresses acute and chronic T. cruzi infection in cyclosporin-treated mice but that gamma interferon is not as effective as the relatively specific antimicrobial ketoconazole. Gamma interferon activates macrophages despite cyclosporin treatment, and its effects appear to be tissue specific.

Acute Disease

Candida albicans septic arthritis and osteomyelitis of the sternoclavicular joint in a patient with human immunodeficiency virus infection.

A 52-year-old intravenous drug user, seropositive for human immunodeficiency virus, developed Candida albicans fungemia and septic phlebitis due to an infected peripheral plastic intravenous catheter. Amphotericin B produced quick resolution of fungemia and systemic toxicity, but in the midst of treatment, after 647 mg of amphotericin B, he developed sternoclavicular osteomyelitis and arthritis due to Candida albicans. He responded well to surgical debridement and continuance of antifungal therapy. This is the only case to our knowledge of Candida albicans arthritis and osteomyelitis occurring either in a patient infected with human immunodeficiency virus or in the sternoclavicular joint.

Arthritis, Infectious

Pneumococcal bacteremia as a marker for human immunodeficiency virus infection in patients without AIDS.

We retrospectively reviewed medical records of all adult patients with blood cultures positive for Streptococcus pneumoniae to determine the number of HIV seropositive patients in whom S pneumoniae bacteremia was the presenting manifestation. We also compared the clinical presentation, laboratory data, and outcome of pneumococcal bacteremia in patients who were HIV seropositive with patients with no risk factors for HIV infection. All adult patients with blood cultures positive for S pneumoniae from January 1987 through April 1989 at two acute care general hospitals in northern California were identified by review of microbiology data. One hospital served veterans, the other the indigent of a suburban area. Six (15%) of 41 patients with pneumococcal bacteremia were HIV seropositive; five were not known to be HIV seropositive before the onset of bacteremia, and the sixth was asymptomatic with respect to HIV infection. No patient with AIDS had pneumococcal bacteremia. HIV seropositive patients were significantly younger, had significantly fewer underlying diseases, and had fewer complications of pneumococcal bacteremia than bacteremic patients with no risk factors for HIV infection. Patients with pneumococcal bacteremia should be evaluated for HIV infection, especially in the absence of other underlying diseases that predispose to pneumococcal bacteremia.

Acquired Immunodeficiency Syndrome

Open trial of cefepime (BMY 28142) for infections in hospitalized patients.

The safety and efficacy of cefepime, a new broad-spectrum, semisynthetic parenteral cephem antibiotic, were evaluated in an open trial at a single hospital. Seventy patients were treated with cefepime: 44 had lower respiratory tract infections, 4 had urinary tract infections, and 22 had skin or soft tissue infections. Of 65 clinically evaluable patients, 64 (98%) had satisfactory responses. No mortality or superinfections occurred. Of 57 respiratory and urinary tract pathogens, 54 (95%) were eradicated and 3 (5%) persisted after therapy. Five bacteremias (two with Streptococcus pneumoniae and one each with Staphylococcus aureus, Proteus mirabilis, and a coagulase-negative staphylococcus) were eradicated. MICs ranged from 1 to 8 micrograms/ml for 13 S. aureus and 9 Pseudomonas aeruginosa isolates and were less than or equal to 0.125 micrograms/ml for 10 streptococcal isolates. Adverse effects occurred in two patients: transient diarrhea and Clostridium difficile toxin in the stool in one patient and loose bowel movements and increased transaminases in the other patient. Cefepime appeared to be well tolerated in humans and was effective against a wide range of isolates, including S. aureus and P. aeruginosa.

Cefepime

Toxicity, immunogenicity, and tumor radioimmunodetecting ability of two human monoclonal antibodies in patients with metastatic colorectal carcinoma.

Two human immunoglobulin M (IgM) monoclonal antibodies (MoAbs), 16.88 and 28A32, which react with cytoplasmic (28A32 and 16.88) or cell surface (28A32) determinants on human colon carcinoma cells, were administered intravenously to 26 patients with metastatic colorectal carcinoma to determine if they could localize to sites of metastatic disease, if they had any antitumor or toxic effects, and to determine whether they would elicit an antihuman MoAb response. Serial scans showed tumor uptake of radioisotope in 12 of 16 patients receiving 131I-labeled 28A32 and in nine of 12 patients receiving 131I-labeled 16.88. No antitumor effects were seen with either antibody. No antibody-related toxic effects were observed following administration of 16.88, but two patients developed localized urticarial reactions following injection with antibody 28A32. No patient developed an antibody response to 16.88. Anti-28A32 reactivity was found in five of 12 (42%) normal sera and in seven of 23 (30%) patients before receiving any antibody. Following administration of 28A32, a low titer (1:10 dilution) of anti-28A32 developed in four patients with no preexisting antibody, a decrease in the preexisting titer was seen in three other patients, the titer remained constant in one patient, and no anti-28A32 was ever detected in six patients. In most cases, anti-28A32 activity was lost at dilutions greater than 1:10 and did not appear to affect antibody half-life in the serum or whole body retention of the antibody. We conclude that these human IgM MoAbs are capable of localizing at sites of disease in vivo, are nontoxic, and are poorly immunogenic in humans. Further studies to determine the specificity of targeting and to improve the delivery of antibody to sites of tumor are indicated.

Antibodies, Monoclonal

The use of butorphanol tartrate for the prevention of canine intussusception following renal transplantation.

Butorphanol tartrate (0.05 mg/kg, im) was included in the preanesthetic medication in 15 out of 29 conditioned female mongrel dogs (22.7-27.3 kg body wt) undergoing renal autotransplants as part of a 48-h kidney preservation study. Four postoperative intussusceptions were noted (3 jejunojejunal, 1 ileocolic) among the 14 dogs without butorphanol, whereas no intussusceptions developed in the 15 dogs receiving butorphanol as part of the preanesthetic protocol. In a prior study, 2 out of 18 dogs undergoing renal autotransplants without the use of butorphanol as part of a 24-h kidney preservation study developed intussusceptions (jejunojejunal). With the exception of butorphanol the anesthetic protocol was the same for all 47 dogs receiving transplants. Throughout these studies the surgical team remained constant, and all dogs were negative for parasites and systemic infectious disease pre- and postoperatively. The results indicate that the use of butorphanol tartrate as part of a preanesthetic protocol is effective in preventing canine intestinal intussusception following renal autotransplantation.

Animals

Human IgM monoclonal antibody 16.88: pharmacokinetics and distribution in mouse and man.

Human IgM monoclonal antibody (MAb) 16.88 recognizes an antigen strongly expressed by colon cancer tissue. We used 131I-labelled 16.88 for biodistribution and pharmacokinetic studies in nude mice bearing WiDr or NIH:OVCAR-3 xenografts. Serum half-life was 8 h. Maximum tumour uptake was between 1 and 8 h after administration and amounted to, respectively, 3% and 1% of the injected dose g-1 for WiDr and NIH:OVCAR-3 tumours. Half-lives in these tumours were approximately 24 h. Tumour to normal colon uptake ratios increased from 2.3 at 24 h to 17 at 5 days after injection. Simultaneously, pharmacokinetic studies were performed in patients with advanced colon cancer reactive with 16.88. They were injected with 5 mCi 131I-16.88 by intravenous infusion over 2 h. Serum half-life was 20 h with greater than 90% of the 131I bound to 16.88. Within 40 h 50% of the injected dose was excreted as free 131I in the urine. In one patient an accelerated clearance was found, possibly caused by pre-existing antibodies reacting with 16.88. None of the patients showed an immune response against 16.88 antibody. Immunoscintigraphy showed positive tumour localization in the majority of the patients, best visualized at later days. We conclude that 16.88 has tumour localization properties while its human origin accounts for the lack of immunogenicity.

Animals