Biomedical subjects
Publications and source records attributed to G Buck.
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In order to establish tumour-specific cytotoxic T lymphocyte (CTL) cell lines, T cells from a human papillomavirus (HPV) type 16-positive patient with a cervical carcinoma in situ and from a healthy volunteer were stimulated in vitro with autologous dendritic cells loaded with peptides derived from the viral transforming proteins E6 and E7 and corresponding to potential HLA-A*0201-restricted T cell epitopes. From each donor a small number of low-affinity CTL lines against the peptide E7/86-93 was obtained, which specifically lysed HLA-A*0201-expressing B-lymphocytes (cell line 721) loaded with this peptide. Cytotoxicity was also observed against two HLA-A*0201-E7-positive epithelial cell lines, the cervical carcinoma cell line CaSki and the HPV-16-immortalized foreskin-keratinocyte cell line HPK IA. However, since none of the CTL recognized both cell lines, and E7-expressing 721 transfectants were never lysed, it was concluded that the reactivity against CaSki and HPK IA cells was due to cross-reactivity on allogeneic HLA molecules rather than to E7 recognition, which emphasizes that the specificity of tumour cell lysis by peptide-induced CTL has to be interpreted with caution.
BACKGROUND: This paper addresses the value of laparoscopic surgery for the removal of gonads in patients with Y-chromosome-bearing gonadal dysgenesis and androgen insensitivity syndrome, who are otherwise faced with a high rate of gonadal malignancy. METHODS: Three patients with Y-chromosome-bearing gonadal dysgenesis and one patient with androgen insensitivity syndrome were operated upon laparoscopically. Removal of gonads was accomplished by their mobilization and dissection from the pelvic side walls, with ligation and transection of the utero-ovarian and infundibulopelvic ligaments. RESULTS: Surgery was without complications. Histological examination of the gonads showed complete removal and absence of malignancy in each patient. Patients were discharged the day after surgery. CONCLUSIONS: The laparoscopic approach is a safe and effective alternative to laparotomy in the management of patients with Y-chromosome-bearing gonadal dysgenesis and with androgen insensitivity syndrome.
This study aimed at investigating the prevalence of osteopenia among a hypoestrogenic group of patients with primary or secondary amenorrhea. Twenty-seven patients with amenorrhea were examined. Sixteen of them presented with secondary amenorrhea (mean age 27.8 +/- 1.9 yrs), and 11 with primary amenorrhea (mean age 21.3 +/- 1.6 yrs). Ten regularly menstruating women (mean age 28.9 +/- 1.4 yrs) served as controls. Estradiol serum levels as well as lumbar spine bone mineral density were measured. All 11 patients with primary amenorrhea showed osteopenia with a mean bone mineral density Z-score of 71 +/- 2% and mean estradiol levels of 30.6 +/- 5.9 pg/ml. The secondary amenorrheic patients were significantly demineralized with a mean Z-score of 82 +/- 3%; 10 of them had osteopenia. Their mean estradiol levels were 34.3 +/- 2.9 pg/ml. The bone density in the primary amenorrheic patients was significantly lower as compared with the secondary amenorrheic women. In comparison, lumbar spine bone density in all control women was normal with a mean Z-score of 104 +/- 3%. In summary, 21 of the 27 patients had osteopenia, higher than that reported in post-menopausal women. Since it is not proven whether the bone mineral deficit of amenorrheic patients can ever be compensated, early diagnostic steps and estrogen-progestogen replacement for the prevention of further bone loss and subsequent fractures are recommended.
Videofluoroscopic modified barium swallow (VMBS) examinations may provide clinically relevant information regarding deglutition in children with cerebral palsy and dysphagia. A retrospective review of clinical evaluations and VMBS studies on 90 consecutive children with cerebral palsy and dysphagia was completed. Most children were referred because of concerns regarding airway protection during oral feedings. Most children had multiple disabilities and 93% were nonambulatory. The majority of children were totally dependent for oral feedings (80%). Oral and pharyngeal phase abnormalities were present in almost all patients. Abnormalities of deglutition were observed only while swallowing specific food textures in the majority of patients. Aspiration of specific food textures was significantly more common than aspiration of all food textures (p < 0.0001). Finally, aspiration was silent in 97% of the patients. VMBS studies can provide clinicians with valuable information regarding the most appropriate food textures and rates of oral feeding for children with cerebral palsy and dysphagia.
Children with neurologically-based dysphagia are at high risk for silent aspiration. Aspiration can lead to complications such as acute pneumonia and chronic lung disease. Thorough evaluation of the oral, pharyngeal, and esophageal phases of swallowing is crucial for patients with dysphagia. The videofluoroscopic modified barium swallow study (MBS) is the procedure of choice for children to delineate the pharyngeal and upper esophageal phases of the swallow that can only be inferred by bedside clinical assessment. This study describes attributes of aspiration and pharyngeal motility in a large sample of infants and children assessed with MBS. Aspiration was observed in 48 (26%) of 186 children, primarily on liquid before or during swallows. Aspiration was trace (less than 10% of a bolus) and silent in 94%. Relationships to clinical history and implications for management are discussed. Given the lack of objective clinical information to identify children at risk for aspiration, MBS should be considered in all children with severe dysphagia to rule out or confirm aspiration.
A case series design was used to identify cases of cystic periventricular leukomalacia (N = 31) identified by neurosonography at one regional tertiary intensive care nursery. Patients were preterm infants born at < or = 32 weeks of gestation who had cysts involving predominantly the middle-posterior or posterior periventricular regions. Neurodevelopmental evaluations were made for 26 (96%) of 27 survivors. All infants assessed had cerebral palsy (i.e., 54% quadriplegia, 42% diplegia, and 4% hemiplegia). Most cognitive delays and all sensory impairments occurred in children with quadriplegia. Periventricular cysts were most extensive on parasagittal, anteroposterior views. The parasagittal, anteroposterior extent of periventricular cysts was most accurate in predicting the type and severity of motor and cognitive disabilities. Quadriplegia was associated with larger and more extensive cysts.
After 15 patients had positive cultures for Mycobacterium abscessus without evidence of infection (i.e., pseudoinfection) following endoscopy, retrospective cohort studies of patients undergoing endoscopy and microbiologic sampling of the environment were done to examine potential nosocomial transmission and to identify the source and risk factors for M. abscessus pseudoinfection. In the epidemic period, M. abscessus-positive cultures were significantly more likely to be obtained during bronchoscopy than gastroendoscopy (16/149 vs. 1/860, P < .001) and during procedures using bronchoscopes disinfected in an automated washer rather than by other methods (16/54 vs. 0/95, P < .001). M. abscessus was recovered from the automated washer, the inlet water feeding the washer, and a flexible bronchoscope. Environmental and case-patient isolates had identical large restriction fragment (LRF) patterns of genomic DNA separated by pulsed-field gel electrophoresis. Molecular typing using LRF analysis supported the epidemiologic results and demonstrate the utility of combined epidemiologic and laboratory investigations in nosocomial outbreaks of nontuberculous mycobacteria.
Selected risk factors for developmental disabilities demonstrate an apparent differential pattern of risk for American Indians as compared to the U.S. general population. Indian children appear to experience comparable or even lower rates of certain congenital anomalies which are associated with developmental disabilities and are difficult to prevent. Conversely, Indians are reported to experience higher rates of conditions which can be effectively targeted for prevention, including those related to prenatal exposure to alcohol, cigarette smoking, and maternal diabetes, as well as disabling sequelae of accidents and otitis media. Primary prevention is critical because of the long-term chronic nature of developmental disabilities and strategies focused on risk factors of particular relevance to Indian communities can achieve the greatest potential benefit.
BACKGROUND: After a 6-year quiescence, methicillin-resistant Staphylococcus aureus (MRSA) was isolated from 30 patients in a children's hospital and a pediatric long-term care facility from November 1987 through April 1989. After six nosocomial cases had occurred at the children's hospital, increased infection control measures directed at MRSA were initiated in August 1988. Because MRSA had been identified in three patients in the pediatric long-term care facility within 24 hours of their admission to the children's hospital, other patients transferred from the pediatric long-term care facility to the children's hospital were isolated and screened for MRSA. METHODS: We reviewed the medical records of these patients and evaluated their response to therapy with rifampin alone or in combination with trimethoprim-sulfamethoxazole. RESULTS: In the 8-month period after initiation of infection control measures, MRSA was identified in 10 residents of the pediatric long-term care facility; there was also one nosocomial children's hospital case. Phage typing showed that one MRSA strain predominated in patients at the pediatric long-term care facility but did not implicate this strain as the source for MRSA introduction into the children's hospital. Of 16 patients with MRSA who completed therapy and were available for follow-up, 13 (81%) had elimination of colonization. CONCLUSION: Prompt institution of MRSA surveillance, barrier isolation, and therapy to eliminate colonization should be considered in hospitals with a new introduction of MRSA.
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We describe here the organization of the ubiquitin genes of the parasitic protozoan Trypanosoma cruzi. T. cruzi contains greater than 100 ubiquitin coding sequences all of which are clustered into a 27 kb segment of the genome. Two types of ubiquitin coding sequences were found. There are five fusion genes (FUS1-5) consisting of a ubiquitin coding sequence fused to a basic non-ubiquitin sequence. The T. cruzi ubiquitin fusion protein is 84% homologous to the product of the UBI gene of Saccharomyces cerevisiae. The non-ubiquitin domains of the two proteins are 67% homologous. There are five polyubiquitin coding genes (PUB) each consisting of varying lengths of polyubiquitin coding sequence and terminating with a single copy of the larger fusion gene. Transcription of the ubiquitin genes results in the generation of six major poly(A)+ mRNAs. The pattern of transcription accurately reflects the genomic organization, in that the transcripts consist of either a single copy of the ubiquitin fusion coding sequence or varying lengths of polyubiquitin (up to 52 copies of the ubiquitin coding unit) each ending with a single copy of the ubiquitin fusion sequence. Finally, there are heat shock elements 5' to the PUB genes and transcription patterns are altered under conditions of stress.
Of 2232 women with no cytologic evidence of intraepithelial neoplasia, 250 (11.2%) were positive for human papillomavirus deoxyribonucleic acid (DNA) by filter in situ hybridization. In 150 of those human papillomavirus-positive patients, an adequate colposcopic examination of the cervix was possible; human papillomavirus infection was diagnosed in 104 women (70%). Cervical cytology showed evidence of human papillomavirus infection in only 23 patients (15%). The following colposcopic features were most common: acetowhite epithelium (29%), punctuation (18%), acetowhite spikes (17%), and mosaicism (9%). Colposcopy was essentially normal in 27%. In 64 hysterectomized patients, vaginal colposcopy showed evidence of human papillomavirus infection in 38 women (59%). Vaginal cytology showed signs of human papillomavirus infection in only 9% (N = 6). Acetowhite spikes were seen in 52%, acetowhite epithelium in 5%, punctuation in 3%, and normal findings in 40%. Histologic examination of 25 biopsy specimens (cervical, N = 15; vaginal, N = 10) showed mainly a lack of glycogenation, acanthosis, and elongation of rete pegs. Koilocytosis and dyskeratosis were seen only in a few cases as rare foci, hence the negative cytology. We conclude that colposcopy is far more sensitive than cytology for the detection of cervical and vaginal human papillomavirus infection.
A patient with a long history of arthritis developed pneumonia. Two weeks into her hospital course, the patient developed effusions in her knee and wrist that yielded cultures positive for Mycoplasma pneumoniae. To our knowledge, this is the third reported case of M pneumoniae isolation from a joint and the first report of isolation of M pneumoniae from two joints in a patient without hypogammaglobulinemia. The evidence suggests that in individuals with atypical pneumonia and joint effusions, M pneumoniae should be considered as a source of infection.
Variant surface glycoprotein (VSG) genes of African trypanosomes are expressed when they are inserted into one of several telomere-linked expression sites. We cloned and characterized an 11-kilobase (kb) DNA fragment located upstream of an expressed VSG gene. A DNA sequence of 1.8 kb that is located immediately upstream of the inserted VSG gene contains sequences homologous to the 76-base-pair repeats described as being upstream of VSG genes in Trypanosoma brucei (D. A. Campbell, M. P. Van Bree, and J. C. Boothroyd, Nucleic Acids Res. 12:2759-2774). There are no such sequences elsewhere in the 11-kb cloned region. Southern blot analysis using probes from the cloned region revealed multiple unlinked copies of the same or very similar regions. At least three of these are located near telomeres, and two have been shown to be used for the expression of known Trypanosoma equiperdum VSG genes. Like VSG genes, the upstream sequences themselves can be duplicated and deleted. The choice of expression site to be used by a duplicated VSG gene is nonrandom; the site used for expression of the parental VSG gene is strongly favored for use in the daughter variant. Furthermore, even when the parental expression site is not used, the VSG gene occupying it is replaced. Thus, an active expression site is a preferential target for gene conversion in the next variation event.
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