Biomedical subjects
M S Edwards
Publications and source records attributed to M S Edwards.
Brain tumor chemotherapy: an evaluation of agents in current use for phase II and III trials.
The reported English-language literature since 1969 on chemotherapy for malignant brain tumors has been collated, and reports of drugs or drug combinations used in phase II or III trials or with adjunctive therapies are reviewed. A significant fraction of the literature contained only anecdotal information, and even in the reports of more systematic trials, the criteria used to evaluate response were variable, ranging from subjective evaluation of clinical improvement to more stringent evaluations using one or more neurodiagnostic tests. A more consistent method of determining response is needed to facilitate comparison of different treatment protocols in the future, and guidelines for this are suggested. It appears that drugs of small molecular size (less than 450 daltons) and high lipid solubility have been the most effective. Single-agent chemotherapy using cell-cycle-specific drugs has, however, been disappointing. The nitrosoureas (especially BCNU) used either singly or in combination have consistently been the most effective agents in phase II and III trials. The combination of irradiation with adjunctive BCNU remains, for the present, the standard against which all other phase II and III protocols should be compared. New drugs for phase II evaluations are sorely needed. There is also need for new combination-drug and sequential-drug protocols for evaluation. The use of radiosensitizing agents with more novel radiation therapy fractionations and in combination with adjunctive drug therapies holds some promise for improving the disappointing results obtained thus far with chemotherapy for malignant brain tumors.
Quantitative observations of the acute effects of X-irradiation on brain capillary permeability: Part I.
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Quantitative observations of the subacute effects of X irradiation on brain capillary permeability: Part II.
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Rapid diagnosis of type III group B streptococcal meningitis by latex particle agglutination.
A latex particle agglutination assay was developed to detect type III group B streptococcal antigen in cerebrospinal fluid. Agglutination was observed in each of 12 initial and 54% of 26 subsequent CSF specimens obtained a mean of 53 hours after the institution of antimicrobial therapy. Latex agglutination was more sensitive than countercurrent immunoelectrophoresis for the detection of type III group B streptococcal antigen in CSF from neonates and young infants with meningitis.
Prospective diagnosis of early onset group B streptococcal infection by countercurrent immunoelectrophoresis.
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Opsonic specificity of human antibody to the type III polysaccharide of group B Streptococcus.
The functional significance of vaccine-induced or naturally acquired antibody to the capsular polysaccharide of type III group B Streptococcus was determined in human sera by means of an opsonophagocytic assay. Sera containing a sufficient concentration of type-specific antibody and endogenous serum complement caused a significant reduction (greater than 1 log10) in colony-forming units for each of 22 type III clinical isolates after incubation for 40 min. In contrast, serum with a very low concentration of antibody (0.4 micrograms/ml) killed only one isolate. Absorption of serum containing vaccine-induced antibody with purified native type III polysaccharide decreased opsonophagocytosis by a mean of 1.2 log10 for 11 selected type III strains. These results indicate a lack of major antigenic differences among a wide spectrum of type III strains, since bactericidal activity of human serum is uniformly observed in the presence of complement and sufficient concentrations of antibody to the type III polysaccharide.
Phase II evaluation of thioTEPA for treatment of central nervous system tumors.
Nineteen patients with primary malignant gliomas were treated with thioTEPA. It was found to be ineffective in 13 evaluable patients.
Predictive value of cerebrospinal fluid polyamines in medulloblastoma.
Seventy-five cerebrospinal fluid polyamine determinations were evaluated in 16 patients with medulloblastoma. Parameters utilized in evaluating patient status for correlation with the polyamine concentrations were neurological examination, computerized tomography, radionuclide scan, myelography, and cerebrospinal fluid cytology. Fifteen of the 16 patients showed absolute correlation with the eventual clinical picture. One determination on one patient resulted in a false negative. No false positives have been observed to date.
An etiologic shift in infantile osteomyelitis: the emergence of the group B streptococcus.
Twenty-one infants from six to 52 days of age (mean 23.3 days) with osteomyelitis were studied between 1965 and 1977. The etiologic agents were group B streptococcus (8), staphylococcus aureus (6), gramnegative bacilli (4), Streptococcus pneumoniae (1), and unknown (2). Patients with group B streptococcal osteomyelitis were characterized by an uncomplicated neonatal course, single bone involvement with a predilection for involvement of the proximal humerus, and lack of inflammatory signs. In contrast, patients with osteomyelitis due to other organisms frequently had had manipulative procedures predisposing to infection and were more likely to have multiple bone involvement, fever, and leukocytosis at the time of diagnosis. Functional impairment was detected in only one of 17 patients evaluated a mean of 36 months after diagnosis.
Acute glossitis due to Hemophilus influenzae type b.
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Mycobacterium terrae synovitis and osteomyelitis.
An immunocompromised patient with Mycobacterium terrae synovitis and osteomyelitis is presented. Therapeutic recommendations are made based upon existing knowledge of the pathogenesis, course, and outcome of similar infections with nontuberculous mycobacteria.
Immunogenicity of polysaccharides from type III, group B Streptococcus.
The immunogenicity and safety of two polysaccharides isolated from type III, group B Streptococcus, were tested in adults selected for existing low concentrations of natural antibody to the capsular polysaccharide of this organism. Both vaccine preparations (trichloroacetic acid and EDTA) were found to lack pyrogenicity and toxicity for experimental animals. A single 50-microgram subcutaneous injection of either polysaccharide in human subjects elicited significant increase in antibody concentration in immunized compared with control individuals receiving phosphate-buffered saline. Antibody responses were maximal by 2 wk and remained at 21 wk after immunization. Vaccine-induced antibody was primarily of the IgG class. Of the two vaccines, the larger molecular size polysaccharide was significantly more immunogenic. Although no systemic reactions were recorded, mild transient local reactions occurred in 45% of vaccinees.
Chemotherapy of recurrent medulloblastoma with combined procarbazine, CCNU, and vincristine.
Seventeen patients with recurrent medulloblastoma were treated with a combination of three drugs: procarbazine, CCNU, and vincristine (PCV). Tumor recurrence was documented at varying periods following surgery and radiotherapy. Among 16 evaluable patients, ten showed a response to PCV on the basis of subjective neurological improvement and a decrease in tumor size by radiological criteria. Five patients were designated as having stable disease on the basis of no change in neurological status and tumor size. One patient showed uninterrupted progression of disease. The median time to progression for all patients was 45 weeks. Significnat myelotoxicity, exacerbated by prior spinal irradiation, compromised therapy. After an initial response, it was often necessary to reduce the higher doses of CCNU and procarbazine that caused concomitant bone-marrow toxicity; as a consequence of the lowered doses, tumor progression was then frequently observed. The authors conclude that PCV is an effective form of palliative therapy for recurrent medulloblastoma.
Pelvic osteomyelitis in children.
Six children (7 to 16 years of age) with pelvic osteomyelitis are described. Sites of involvement included the pubis in three patients, the ilium in two patients, and the ischium in one patient. All were right-sided. Each patient presented with a history of fever and an abnormal gait. In four, the point tenderness indicated the site of bony involvement. All patients had pain on abduction but free passive range of motion of the hip. Soft tissue swelling was present on admission pelvic roentgenograms in five patients. Intravenous pyelogram revealed deviation of the bladder toward the midline in each of four patients studied. Roentgenographic changes typical of osteomyelitis developed in four patients ten days to ten weeks after onset of symptoms. In four patients in whom an organism was identified, Staphylococcus aureus was isolated from blood and/or bone. All isolates were methicillin-sensitive and two were penicillin-sensitive. Purulent material was drained from three of the five patients who underwent surgical exploration of the pelvis. All patients received parenteral antistaphylococcal therapy for 3 to 5 1/2 weeks (mean, 4 weeks). Oral antibiotics were given to five patients for an additional 3 to 14 weeks. All patients recovered completely.
Cavernous sinus syndrome produced by communication between the external carotid artery and cavernous sinus.
The authors present two cases of cavernous sinus syndrome with spontaneous onset secondary to arteriovenous malformations and review the cases reported previously. These malformations enlarge slowly and produce symptoms only in adult life. Diagnosis may be difficult when there is no associated bruit. Adequate evaluation necessitates selective angiography of both the internal and external carotid artery circulation and the vertebral circulation. Conservative treatment is recommended unless symptoms worsen or there is progressive loss of vision.
Dissociation of MSH and ACTH release in man.
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Hepatitis and epidemic hepatitis associated antigen (E.H.A.A.) in a haemodialysis unit with observations on haemoglobin levels.
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