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1.  Fluoroquinolone exposure prior to tuberculosis diagnosis is associated with an increased risk of death 
Fluoroquinolone (FQ) exposure before tuberculosis (TB) diagnosis is common, but its effect on outcomes, including mortality, is unclear.
Among TB patients reported to the Tennessee Department of Health from 2007 to 2009, we assessed FQ exposure within 6 months before TB diagnosis. The primary outcome was the combined endpoint of death at the time of TB diagnosis and during anti-tuberculosis treatment.
Among 609 TB cases, 214 (35%) received FQs within 6 months before TB diagnosis. A total of 71 (12%) persons died; 10 (2%) were dead at TB diagnosis and 61 (10%) died during anti-tuberculosis treatment. In multivariable logistic regression analysis, factors independently associated with death were older age (OR 1.05 per year, 95%CI 1.04–1.07), human immunodeficiency virus infection (OR 8.08, 95%CI 3.83–17.06), US birth (OR 3.03, 95%CI 1.03–9.09), and any FQ exposure before TB diagnosis (OR 1.82, 95%CI 1.05–3.15). Persons with FQ exposure before TB diagnosis were more likely to have culture- and smear-positive disease than unexposed persons.
Among this patient population, FQ exposure before TB diagnosis was associated with an increased risk of death. These findings underscore the need for cautious use of FQs in persons with possible TB.
PMCID: PMC3981533  PMID: 22794509
drug-susceptible TB; drug resistance; mortality
2.  Deficiencies in current childhood immunization indicators. 
Public Health Reports  1998;113(6):527-532.
OBJECTIVE: To investigate "up-to-date" and "age-appropriate" indicators of preschool vaccination status and their implications for vaccination policy. METHODS: The authors analyzed medical records data from the Baltimore Immunization Study for 525 2-year-olds born from August 1988 through March 1989 to mothers living in low-income Census tracts of the city of Baltimore. RESULTS: While only 54% of 24-month-old children were up-to-date for the primary series, indicators of up-to-date coverage were consistently higher, by 37 or more percentage points, than corresponding age-appropriate indicators. Almost 80% of children who failed to receive the first dose of DTP or OPV age-appropriately failed to be up-to-date by 24 months of age for the primary series. CONCLUSIONS: Age-appropriate immunization indicators more accurately reflect adequacy of protection for preschoolers than up-to-date indicators at both the individual and population levels. Age-appropriate receipt of the first dose of DTP should be monitored to identify children likely to be underimmunized. Age-appropriate indicators should also be incorporated as vaccination coverage estimators in population-based surveys and as quality of care indicators for managed care organizations. These changes would require accurate dates for each vaccination and support the need to develop population-based registries.
PMCID: PMC1308436  PMID: 9847924
3.  Estimating vaccination coverage using parental recall, vaccination cards, and medical records. 
Public Health Reports  1998;113(6):521-526.
OBJECTIVE: To compare estimates based on vaccination cards, parental recall, and medical records of the percentages of children up-to-date on vaccinations for diphtheria, tetanus, and pertussis; polio; and measles, mumps, and rubella. METHOD: The authors analyzed parent interview and medical records data from the Baltimore Immunization Study for 525 2-year-olds born from August 1988 through March 1989 to mothers living in low-income Census tracts of the city of Baltimore. RESULTS: Only one-third of children had vaccination cards; based on medical records, these children had higher up-to-date coverage at 24 months of age than did children without cards. For individual vaccines, only two-thirds of parents could provide information to calculate coverage rates; however, almost all provided enough information to estimate coverage for the primary series. For each vaccine and the series, parental recall estimates were at least 17 percentage points higher than estimates from medical records. For children without vaccination cards whose parents could not provide coverage information, up-to-date rates based on medical records were consistently lower than for children with cards or with parents who provided coverage information. CONCLUSIONS: Population-based vaccine coverage surveys that rely on vaccination cards or parental recall or both may overestimate vaccination coverage.
PMCID: PMC1308435  PMID: 9847923
4.  Regulation of telomerase activity in immortal cell lines. 
Molecular and Cellular Biology  1996;16(6):2932-2939.
Telomerase is a ribonucleoprotein whose activity has been detected in germ line cells, immortal cells, and most cancer cells. Except in stem cells, which have a low level of telomerase activity, its activity is absent from normal somatic tissues. Understanding the regulation of telomerase activity is critical for the development of potential tools for the diagnosis and treatment of cancer. Using the telomeric repeat amplification protocol, we found that immortal, telomerase-positive, pseudodiploid human cells (HT1080 and HL60 cells) sorted by flow repressed in quiescent cells. This was true whether quiescence was induced by contact inhibition (NIH 3T3 mouse cells), growth factor removal (bromodeoxyuridine-blocked mouse myoblasts), reexpression of cellular senescence (the reversibly immortalized IDH4 cells), or irreversible cell differentiation (HL60 promyelocytic leukemia cells and C2C12 mouse myoblasts). Taken together, these results indicate that telomerase is active throughout the cell in dividing, immortal cells but that its activity is repressed in cells that exit the cell cycle. This suggests that quiescent stem cells that have the potential to express telomerase may remain unaffected by potential antitelomerase cancer therapies.
PMCID: PMC231287  PMID: 8649404
5.  Mutational analysis of the 18-base-pair inverted repeat element at the bovine papillomavirus origin of replication: identification of critical sequences for E1 binding and in vivo replication. 
Journal of Virology  1995;69(10):6525-6532.
Replication of bovine papillomavirus requires two viral proteins, E1 and E2-TA. Previously we demonstrated that sequences within an imperfect 18-bp inverted repeat (IR) element were sufficient to confer specific binding of the E1 protein to the origin region (S. E. Holt, G. Schuller, and V. G. Wilson, J. Virol. 68:1094-1102, 1994). To identify critical nucleotides for E1 binding and origin function, a series of individual point mutations was constructed at each nucleotide position in the 18-bp IR. Binding of E1 to these point mutations established that both the position of the mutation and the specific nucleotide change were important for the E1-DNA interaction. Equivalent mutations from each half of the IR exhibited similar binding, suggesting that the halves were functionally symmetric for E1 interactions. Each of these mutations was evaluated also for origin function in vivo by a transient-replication assay. No single point mutation eliminated replication capacity completely, though many mutants were severely impaired, demonstrating an important functional contribution for the E1 binding site. Furthermore, E1 binding was not sufficient for replication, as several origin mutants bound E1 well in vitro but replicated poorly in vivo. This suggests that certain nucleotides within the 18-bp IR may be involved in postbinding events necessary for replication initiation. The results with the point mutations suggest that E1-E1 interactions are important for stable complex formation and also indicate that there is some flexibility with regard to formation of a functional E1 replication complex at the origin.
PMCID: PMC189554  PMID: 7666554
6.  DNA binding specificity of the bovine papillomavirus E1 protein is determined by sequences contained within an 18-base-pair inverted repeat element at the origin of replication. 
Journal of Virology  1994;68(2):1094-1102.
Bovine papillomavirus type 1 (BPV-1) DNA replicates episomally and requires two virally expressed proteins, E1 and E2, for this process. Both proteins bind to the BPV-1 genome in the region that functions as the origin of replication. The binding sequences for the E2 protein have been characterized previously, but little is known about critical sequence requirements for E1 binding. Using a bacterially expressed E1 fusion protein, we examined binding of the BPV-1 E1 protein to the origin region. E1 strongly protected a 28-bp segment of the origin (nucleotides 7932 to 15) from both DNase I and exonuclease III digestion. Additional exonuclease III protection was observed beyond the core region on both the 5' and 3' sides, suggesting that E1 interacted with more distal sequences as well. Within the 28-bp protected core, there were two overlapping imperfect inverted repeats (IR), one of 27 bp and one of 18 bp. We show that sequences within the smaller, 18-bp IR element were sufficient for specific recognition of DNA by E1 and that additional BPV-1 sequences beyond the 18-bp IR element did not significantly increase origin binding by E1 protein. While the 18-bp IR element contained sequences sufficient for specific binding by E1, E1 did not form a stable complex with just the isolated 18-bp element. Formation of a detectable E1-DNA complex required that the 18-bp IR be flanked by additional DNA sequences. Furthermore, binding of E1 to DNA containing the 18-bp IR increased as a function of overall increasing fragment length. We conclude that E1-DNA interactions outside the boundaries of the 18-bp IR are important for thermodynamic stabilization of the E1-DNA complex. However, since the flanking sequences need not be derived from BPV-1, these distal E1-DNA interactions are not sequence specific. Comparison of the 18-bp IR from BPV-1 with the corresponding region from other papillomaviruses revealed a symmetric conserved consensus sequence, T-RY--TTAA--RY-A, that may reflect the specific nucleotides critical for E1-DNA recognition.
PMCID: PMC236548  PMID: 8289339
7.  A randomised trial comparing endometrial resection and abdominal hysterectomy for the treatment of menorrhagia. 
BMJ : British Medical Journal  1991;303(6814):1362-1364.
OBJECTIVE--To determine the advantages and disadvantages of endometrial resection and abdominal hysterectomy for the surgical treatment of women with menorrhagia. DESIGN--Randomised study of two treatment groups with a minimum follow up of nine months. SETTING--Royal Berkshire Hospital, Reading. SUBJECTS--51 of 78 menorrhagic women without pelvic pathology who were on the waiting list for abdominal hysterectomy. TREATMENT--Endometrial resection or abdominal hysterectomy (according to randomisation). Endometrial resections were performed by an experienced hysteroscopic surgeon; hysterectomies were performed by two other gynaecological surgeons. MAIN OUTCOME MEASURES--Length of operating time, hospitalisation, recovery; cost of surgery; short term results of endometrial resection. RESULTS--Operating time was shorter for endometrial resection (median 30 (range 20-47) minutes) than for hysterectomy (50 (39-74) minutes). The hospital stay for endometrial resection (median 1 (range 1-3) days) was less than for hysterectomy (7 (5-12) days). Recovery after endometrial resection (median 16 (range 5-62) days) was shorter than after hysterectomy (58 (11-125) days). The cost was 407 pounds for endometrial resection and 1270 pounds for abdominal hysterectomy. Four women (16%) who did not have an acceptable improvement in symptoms after endometrial resection had repeat resections. No woman has required hysterectomy during a mean follow up of one year. CONCLUSION--For women with menorrhagia who have no pelvic pathology endometrial resection is a useful alternative to abdominal hysterectomy, with many short term benefits. Larger numbers and a longer follow up are needed to estimate the incidence of complications and the long term efficacy of endometrial resection.
PMCID: PMC1671634  PMID: 1760601
8.  Community obstetric care in West Berkshire. 
BMJ : British Medical Journal  1991;302(6778):698-700.
OBJECTIVE--To assess the effects of a revised obstetric booking policy whereby all low risk pregnant women received their antenatal care entirely in the community. DESIGN--Comparison of the distribution of antenatal clinic attendances, transfers, and perinatal mortality rates for 1987 and 1989, before and after introduction of the revised policy. SETTING--West Berkshire Health District. SUBJECTS--All women who delivered with a registrable birth in the district in 1987 (5817 women) and 1989 (5372). MAIN OUTCOME MEASURES--Attendances at community and consultant antenatal clinics; bookings transferred from community care to consultant care; perinatal mortality rates. RESULTS--Of 5372 women delivering in West Berkshire in 1989, 3185 (58.3%) were originally booked for general practitioner-midwife care, of whom 1567 (49.2% of general practitioner-midwife bookings) were transferred to consultant care. 1618 women (30.1% of all women delivered) received their entire obstetric care from general practitioners and midwives. Attendance at hospital antenatal clinics was reduced by 16%. In 1989 the perinatal mortality rates (1987 values) for the district were 6.3 (7.6) per 1000 births overall; 8.2 (8.3) per 1000 consultant bookings; 5.0 (4.7) per 1000 for community bookings; and 10.2 (14.4) per 1000 for women transferred to consultant care. CONCLUSION--Antenatal care of low risk pregnant women may safely be provided by their general practitioner and midwife.
PMCID: PMC1669136  PMID: 1878023
10.  Contaminated hospital water supplies. 
British Medical Journal  1979;1(6177):1564-1565.
PMCID: PMC1599657  PMID: 466125
11.  Selective and enhanced recovery of group A and B streptococci from throat cultures with sheep blood agar containing sulfamethoxazole and trimethoprim. 
Journal of Clinical Microbiology  1977;5(6):650-655.
Sheep blood agar containing 23.75 microgram of sulfamethoxazole and 1.25 microgram of trimethoprim (SXT-BA) per ml was compared with conventional sheep blood agar (SBA) for isolating group A and B streptococci from throat cultures. This selective medium allowed much better recovery of group A and B streptococci and suppressed the growth of the normal flora, including "viridans" streptococci. In an initial study of 700 throat cultures, SXT-BA recovered 42% more group A and 49% more group B streptococci than did SBA. When SXT-BA was introduced into the routine microbiology laboratory and used by a number of medical technologists. SXT-BA recovered 28% more group A and 37% more group B streptococci than did SBA. In addition, the selective medium inhibited 83% of the non-group A and B streptococci that were recovered by SBA.
PMCID: PMC274672  PMID: 328529
12.  Interauterine Transfusion: 101 Consecutive Cases treated at Queen Charlotte's Maternity Hospital 
British Medical Journal  1973;3(5870):39-43.
Intrauterine transfusion was performed or attempted in 101 cases during a period of four and a half years. After exclusion of six cases, for reasons detailed in the text, 95 cases are considered in detail. Intrauterine transfusion was successfully performed in 93 of these, with a mean of 2·8 transfusions each. Forty-four babies (46·3%) survived and all but one are so far developing normally.
PMCID: PMC1587950  PMID: 4717424

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