Induction of glioblastoma multiforme in nonhuman primates after therapeutic doses of fractionated whole-brain radiation therapy.

OBJECT: To determine the acute and long-term effects of a therapeutic dose of brain radiation in a primate model, the authors studied the clinical, laboratory, neuroimaging, molecular, and histological outcomes in rhesus monkeys that had received fractionated whole-brain radiation therapy (WBRT). METHODS: Twelve 3-year-old male primates (Macaca mulatta) underwent fractionated WBRT (350 cGy for 5 days/week for 2 weeks, total dose 3500 cGy). Animals were followed clinically and with laboratory studies and serial magnetic resonance (MR) imaging. They were killed when they developed medical problems or neurological symptoms, lesions appeared on MR imaging, or at study completion. Gross, histological, and molecular analyses were then performed. Nine (82%) of 11 animals that underwent long-term follow up (> 2.5 years) developed neurological symptoms and/or enhancing lesions on MR imaging, which were defined as glioblastoma multiforme (GBM), 2.9 to 8.3 years after radiation therapy. The GBMs were categorized as either unifocal (three) or multifocal (six), and were located in the supratentorial (six), infratentorial (two), or both (one) cranial regions. Histological examination revealed distant, noncontiguous tumor invasion within the white matter of all nine animals harboring GBMs. Novel interspecies comparative genomic hybridization (three animals) uniformly showed deletions in the GBMs that corresponded to chromosome 9 in humans. CONCLUSIONS: The high rate of GBM formation (82%) following a therapeutic dose of WBRT in nonhuman primates indicates that radioinduction of these neoplasms as a late complication of this therapy may occur more frequently than is currently recognized in human patients. The development of these tumors while monitoring the monkeys' conditions with clinical and serial MR imaging studies, and access to the tumor and the entire brain for histological and molecular analyses offers an opportunity to gather unique insights into the nature and development of GBMs.

Gallbladder stones analyzes, bile and wound cultures in cholelithiasis.

One hundred and fifty-two consecutive cases of cholelithiasis were studied. The gallbladder stones were analyzed to determine the constituents, the bile specimens were cultured and correlated with the cultures when wound infection occurred. Mixed gallstones were the commonest type (58.5%), pigment stones (27%) and cholesterol stones (14.5%). Positive bile cultures were found in 41 patients (27%) and Escherichia coli was the commonest organism isolated. The rate of wound infection was 14.5% and the most common organism cultured from the wound was staphylococcus epidermidis.

Convection-enhanced delivery of macromolecules in the brain.

For many compounds (neurotrophic factors, antibodies, growth factors, genetic vectors, enzymes) slow diffusion in the brain severely limits drug distribution and effect after direct drug administration into brain parenchyma. We investigated convection as a means to enhance the distribution of the large and small molecules 111In-labeled transferrin (111In-Tf; M(r), 80,000) and [14C]sucrose (M(r), 359) over centimeter distances by maintaining a pressure gradient during interstitial infusion into white matter to generate bulk flow through the brain interstitium. The volume of distribution (Vd) containing > or = 1% concentration of infusion solution increased linearly with the infusion volume (Vi) for 111In-Tf(Vd/Vi, 6:1) and [14C]sucrose (Vd/Vi, 13:1). Twenty-four hours after infusion, the distribution of 111In-Tf was increased and more homogeneous, and penetration into gray matter had occurred. By using convection to supplement simple diffusion, enhanced distribution of large and small molecules can be obtained in the brain while achieving drug concentrations orders of magnitude greater than systemic levels.

Peripheral benzodiazepine receptors and glucose metabolism in human gliomas.

Peripheral benzodiazepine receptors (PBR) are increased in gliomas and augmented glucose metabolism is seen in malignant brain tumors. We investigated the relationship between PBR density (Bmax) and glucose utilization rate (GUR) in 17 patients with cerebral gliomas of different grades. PBR Bmax was assessed by [3H]PK-11195 in vitro binding in surgical specimens and GUR was measured by Positron Emission Tomography with [18F]2-Fluorodeoxyglucose before the surgery. In untreated tumors there was a positive correlation between PBR Bmax and GUR (2r = 0.84). This correlation was not observed in patients who had been treated with radiation and/or chemotherapy prior to surgery (r2 = 0.13). In addition, in untreated patients, the increase in PBR density and GUR appeared to be related to the degree of malignancy.

Fatal lipoid pneumonia in an infant complicated by Mycobacterium fortuitum infection.

We report a fatal case of lipoid pneumonia in a two and one half month old Saudi female caused by aspiration of animal fat, ghee and complicated by Mycobacterium fortuitum infection. It highlights the need to look for M. fortuitum in lipoid pneumonia and suggests the prevention of the condition through health education.

A study of the knowledge, attitude and practice (KAP) of a Saudi Arabian community towards the problem of brucellosis.

The present study included 337 patients, presenting to Asir Central Hospital with fever of more than two weeks duration, or symptoms associated with brucellosis but without fever. Of the 337 subjects examined for knowledge about methods and means of transmission of brucellosis, 309 (92%) were ignorant while only 28 (8%) appeared to possess some knowledge as to the source, type of animal contact and presentation of illness. None of the 337 subjects was able to link the disease with a microbial infection. The most important common practices associated with brucellosis included raw milk consumption, close animal contact and the slaughtering and disposal of wastes. Illiteracy, ignorance and faulty behaviours emphasize the importance of health education of the community, to raise the KAP standard of the full spectrum of brucellosis in the community would be valuable in its prevention and control.

Valproic acid-associated pancreatitis: report of three cases and a brief review.

We describe three patients with seizure disorders in whom pancreatitis or pancreatic injury was probably caused by valproic acid, a widely used anticonvulsant drug. Trivial or no increases of serum amylase (EC 3.2.1.1) but striking increases of serum lipase (EC 3.1.1.3) were common to all patients, as assayed in the Kodak Ektachem. In vitro, valproic acid does not cause any change in serum lipase. In patients with symptoms suggestive of pancreatitis and abnormal values for amylase and (or) lipase, treatment with valproic acid should be discontinued.

Clinically silent polymicrobial amnionitis and intrauterine fetal death associated with a Cu-7 intrauterine contraceptive device.

PIP: This article presents a case of silent polymicrobial amnionitis with subsequent intrauterine fetal death in a 34-year old woman who conceived with a Cu-7 IUD in place. There were no apparent pregnancy complications or symptoms of uterine infection during early pregnancy. At 16 weeks gestation, the patient underwent amniocentesis for cytogenetic studies. 5 different microorganisms--Corynebacterium, Staphylococcus warneri, Staphylococcus epidermidis, Streptococcus mitis, and Ureaplasma urealyticum--were isolated from the amniotic fluid. 2 week later, intrauterine fetal death was detected. U. urealyticum was at this point isolated from the cervix and placental and fetal tissues. This organism, which has been associated with chorioamnionitis, spontaneous abortion, and neonatal death, is suspected to have contributed to the fetal death in this case. U. urealyticum can invade the amniotic sac with fetal membranes intact and persist for 8 weeks without overt effects. This case illustrates the risks associated with nonremoval of an IUD after contraceptive failure.^ieng

Avulsion fractures of the tibial tubercle in adolescents. A report of bilateral fractures and a review of the literature.

Avulsion fractures of the tibial tubercle prior to epiphyseal closure are being treated with greater frequency. Watson-Jones Types I and III fractures are the most common; both require open reduction and internal fixation. Type II fractures respond to closed reduction and plaster immobilization. The authors have found only 76 fractures reported in the literature since 1935. Four cases were bilateral. Fifty-nine patients were boys, and two were girls; the sex was not reported for 11 patients. Type III fractures occurred most often in older adolescents. Types I and II fractures occurred in younger patients. No reports of growth disturbance of the proximal tibial epiphysis occurring after a Type III fracture were found.

Abnormal lipid accumulation within the small intestinal mucosa of children with juvenile-onset diabetes mellitus.

The lipid content of the proximal jejunum, as studied by light microscopy with lipid histochemical staining methods, is determined in 14 fasting children with juvenile-onset diabetes mellitus. The results show that four children had greatly increased amounts of lipid, while six others had a mildly to moderately increased amounts of lipid present. The amount of lipid present appears to correlate most closely with the quality of control of the diabetes. These results indicate either that the clearance of exogenous lipid is impaired or that there is an increased endogenous synthesis of lipid within the intestine of the diabetic child, especially in those under poor control.

Unidentified gram-negative rod infection. A new disease of man.

A Gram-negative bacillus that defies identification was isolated from blood cultures of 17 patients with fever. Fifteen patients were male adults, and 14 patients had underlying diseases, including previous splenectomy in five, which impair host defenses against infection. Illnesses occurred in the summer and autumn in 14 cases and had been recently preceded by dog bites in 10 cases. Clincal syndromes included cellulitis in seven cases, primary bacteremia without localization in four, purulent meningitis in four, and endocarditis in three. Three patients died. The organism grows slowly on blood or chocolate agar in 10% CO, is oxidase- and catalase-positive, and is negative for nitrate reduction, indole production, and urease. It produces acid from glucose, lactose, and maltose. These features distinguish it from all previously described and classified bacteria. Furthermore, the epidemiologic features of the patients suggest that this organism is an opportunistic invader and may have an animal reservoir in nature.

Detection of Serratia outbreaks in hospital.

Infections due to Serratia marcescens were studied in 23 different hospitals. A retrospective study was done in 4 hospitals; all isolates were compared by serological typing, antibiograms, bacteriocin production, and bacteriocin sensitivity. 2 of the hospitals were having cross-infection problems due to antibiotic-resistant strains, but the other 2 had little or no cross-infection. Outbreaks were studied in 19 other hospitals. 9 of these outbreaks were classified as "common source" since contaminated "sterile solutions" were incriminated as the cause in each. One hospital had a "pseudo-outbreak," in which Serratia from E.D.T.A. blood-collecting tubes contaminated blood-cultures as they were collected. All 10 of these strains from common-source outbreaks were generally sensitive to antibiotics. Outbreaks in 9 other hospitals resulted from cross-infection and were caused by strains which were very resistant to antibiotics. Guidelines for detecting outbreaks are given and control measures are suggested.

A previously undescribed gram-negative bacillus causing septicemia and meningitis.

This report describes a case of septicemia and meningitis secondary to dog bites by two different dogs on two consecutive days. The case is noteworthy because of the unusual characteristics of the etiologic agent and the inability to place the etiologic agent into any currently defined genus or to identify it by the existing systems of classification. The organism is a small, thin, Gram-negative bacillus after 24 hours of incubation on blood agar; after prolonged incubation, it becomes filamentous. The organism is catalase- and oxidase-positive, hydrolyzes esculin, and forms acid in glucose, xylose, and maltose after 21 days' incubation. The organism does not manifest lysis on sheep blood agar, and does not grow on MacConkey, Salmonella-Shigella, Centrimide, nutrient, or Kligler iron agars. The tests for urea, nitrate reduction, and indol are negative. The unidentified Gram-negative bacillus showed susceptibility to all antimicrobials tested except gentamicin.

Reye syndrome: treatment by exchange transfusion with special reference to the 1974 epidemic in Cincinnati, Ohio.

The treatment of 66 children with Reye syndrome proved by hepatic biopsy or autopsy is described. Prior to the utilization of exchange transfusion early in the course of the disease, our case fatality rate was 100% of nine patients. With early diagnosis and early exchange transfusion, the case fatality rate was reduced to 27% of 44 patients. During the 1974 epidemic of Reye syndrome, 26 children were treated. In 18 children the diagnosis was established by hepatic biopsy; 16 received one or more exchange transfusions. There were no deaths among these 26 patients. In the 1974 epidemic, the national case fatality rate was estimated to be 40%. Exchange transfusion appears to have been an important factor in the reduction of the case fatality rate among our patients.

Nursery outbreak of Pseudomonas aeruginosa: epidemiological conclusions from five different typing methods.

In April 1971, nine cases of Pseudomonas aeruginosa septicemia occurred in a high-risk nursery. The epidemiology of the outbreak was studied by pyocin production, pyocin sensitivity, serological typing, antibiotic susceptibility, and phenotypic properties such as colonial morphology, pigment, and hemolysis. Ten isolates of P. aeruginosa were recovered from 9 newborn infants and from 13 environmental sources. Twenty-one of the 23 isolates had identical pyocin production patterns against 60 different indicator strains and were of the same serotype. These 21 isolates were designated as the "outbreak strain"; the other 2 isolates had no epidemiological significance. The results of pyocin sensitivity, antibiotic susceptibility tests, and phenotypic properties were dissimilar. They would yield incorrect epidemiological conclusions if used alone. The outbreak strain dissociated in vitro and these phenotypic changes accounted for the variable results by the latter three typing methods. Although the precise mode of introduction of the organism into the nursery could not be determined in retrospect, the epidemiological data strongly suggested that one infant contracted a P. aeruginosa infection, and this strain spread throughout the nursery by means of contaminated resuscitation equipment.

Effect of antibiotic treatment on the incidence of infectious drug resistance among intestinal lactose-fermenting bacteria isolated from burn patients.

Antibiotic-resistant lactose-fermenting bacteria were recovered from the feces of 20 of 25 burn patients studied. Of the Escherichia coli isolated from patients receiving antibiotic treatment, 81.5% were shown to be infectiously resistant; only 32% of the E. coli recovered from patients not receiving antibiotics were shown to be harboring R factors. Three resistance patterns, ampicillin-chloramphenicol-streptomycin-kanamycin, ampicillin-tetracycline, and ampicillin-streptomycin, accounted for 25.2, 20.3, and 15.4%, respectively, of the total R factors identified.