tbuckley/cabot-search huggingface dataset:
Synergistic effect of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic porphyrin levels in the rat.
Authors: A P van Birgelen, K M Fase, J van der Kolk, H Poiger, A Brouwer, W Seinen, M van den Berg
Journal: Environmental Health Perspectives (1996)

We studied the effect of polychlorinated biphenyls (PCBs) on hepatic porphyrin accumulation in female Sprague-Dawley rats by feeding them diets containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), or combinations of the single PCB congeners with TCDD for 13 weeks. A dose-dependent increase in hepatic porphyrin accumulation occurred after TCDD, PCB 126, or PCB 156 administration, reaching maximal levels of about twice control values. The lowest dose levels for which a significant increase in hepatic porphyrin accumulation was found were 0.7 microgram TCDD/kg diet, 50 micrograms PCB 126/kg diet, or 6 mg PCB 156/kg diet. These doses are equivalent to 47 ng TCDD/kg/day, 3.2 micrograms PCB 126/kg/day, and 365 micrograms PCB 156/kg/day. Relative potencies for hepatic porphyrin accumulation, using TCDD as a reference, ranged from 0.015 to 0.06 for PCB 126 and from 0.0001 to 0.0003 for PCB 156. CYP1A2 activities significantly correlated with hepatic porphyrin levels, with coefficients of 0.629, 0.483, or 0.808 for TCDD, PCB 126, or PCB 156, respectively. Administration of PCB 153 alone did not result in hepatic porphyrin accumulation. Co-administration of PCB 153 and TCDD revealed a strong synergistic effect on porphyrin accumulation (about 800 times control levels). This synergistic effect was significant in rats fed diets containing any combination of PCB 153 with TCDD. Uroporphyrin III and heptacarboxylic porphyrin were accumulated in porphyrinogenic livers. These results suggest that TCDD induction of CYP1A2 may be involved, leading to oxidation of uroporphyrinogen III to uroporphyrin III, in combination with an increase in delta-aminolevulinic acid synthetase induced by PCB 153. Under porphyrinogenic conditions, an inhibitor of CYP1A2 activity may also be formed. The interactive effects on porphyrin accumulation after co-administration of dioxinlike and non-dioxinlike compounds may have significant implications for the risk assessment of these chemicals.
Gastrointestinal endoscopy: some perspectives.
Authors: A K Grant, H A Harley
Journal: BMJ (1982)

Remarkable technological advances of fibreoptic endoscopy in the past two decades have produced important improvements in diagnosis and treatment of gastrointestinal and hepatobiliary disorders. These advances must be kept in perspective; continuing, critical assessment of their contribution to the management of patients is desirable. Endoscopy can have adverse effects on the total performance of departments of gastroenterology, on gastroenterology as a discipline, and even on the status of the medical profession in the community. Gastroenterologists need to show proficiency of performance and integrity of practice. Control may be achieved by certification delineation of privileges, peer review, public accountability, and realistic financial returns for procedures. Records of a department of gastroenterology indicate that some control may be achieved by insistence on a consultation before decision on endoscopy. This may be a desirable alternative to endoscopy on demand. Undue emphasis on technology runs some risk of destroying the proper practice of consultant medicine.
Revival of the Senning operation in the treatment of transposition of the great arteries. Preliminary report on recent experience.
Authors: J M Quaegebeur, J Rohmer, A G Brom
Journal: Thorax (1977)

This preliminary report presents recent experience with the Senning operation for transposition of the great arteries. Reasons are given why the traditional Mustard procedure was abandoned in favour of the Senning operation. Technical details are presented and the advantages and disadvantages of the procedure are discussed.
Activation of Heat-Shock Factor by Stretch-Activated Channels in Rat Hearts
Authors: Jiang Chang, Jeremy S. Wasser, Richard N.M. Cornelussen, A.A. Knowlton
Journal: Circulation (2001)

Background — Previously, we have observed that the isolated, erythrocyte-perfused rabbit heart has increased levels of heat-shock protein (HSP) 72 after a mild mechanical stress. We hypothesized that stretch-activated ion channels (SACs) mediated this increase. Methods and Results — To test this hypothesis, we subjected isolated, perfused rat hearts to mechanical stretch. Gel mobility shift assay showed that heat-shock factor (HSF) was activated in hearts with mechanical stretch, but not in controls. Supershift experiments demonstrated that HSF1 was the transcription factor. Northern blots revealed the concomitant increase in HSP72 mRNA in stretched rat hearts. In a separate set of experiments, gadolinium, an inhibitor of SACs, was added to the perfusate. Gadolinium inhibited the activation of HSF and decreased HSP72 mRNA level. Because gadolinium can inhibit both SACs and L-type calcium channels, we perfused a group of hearts with diltiazem, a specific L-type calcium channel blocker, to eliminate the involvement of L-type calcium channels. Diltiazem failed to inhibit the activation of HSF. Conclusions — Stretch in the rat heart results in activation of HSF1 and an increase in HSP72 mRNA through SACs. This represents a novel mechanism of HSF activation and may be an important cardiac signaling pathway for hemodynamic stress.
A Huge Osteophyte in the Sacroiliac Joint Appearance on Bone SPECT
Authors: EINAT EVEN-SAPIR, ROBERT H. MARTIN, MICHAEL J. MITCHELL
Journal: Clinical Nuclear Medicine (1994)

Bone scintigraphy was performed in a patient with cancer who had recent pain over the left sacroiliac region. Planar images detected a focal area of increased uptake thought to be a metastasis to the left sacroiliac joint. SPECT imaging showed that the lesion extended anteriorly beyond the bone margins, but, on CT imaging, showed it to be a huge osteophyte bridging the left sacroiliac joint. A lesion that extends beyond the bone margins, as seen in this case, has been previously described in SPECT of osteophytes in vertebrae and appears to be a typical SPECT finding of osteophytosis. SPECT may be helpful in differentiating osteophytes from metastases.
There’s More to a PEG Than Just Putting One In
Authors: W. L. Berger
Journal: Endoscopy (2002)

We are no longer fascinated and amazed by the mere fact that a PEG can be done. First, blindly open a tract across multiple fascial planes and intentionally perforate hollow viscera, producing a pneumoperitoneum, and relying only on “sutureless approximation” for tract stability. Then (literally adding insult to injury) coat a foreign body with saliva and insert it into this fresh wound. In the 1980s, critics were sincerely convinced that this could lead only to disaster [1]. If it had not been conceived, developed, and tirelessly championed by well-respected academic surgeons [2], this counterintuitive shortcut technique, which seemingly violates every surgical principle, might have passed quietly into disreputable obscurity. Our view today is quite different, of course; now, we are only amazed that we ever regarded this simple procedure with suspicion.
A counsellor in every practice?
Authors: M Pringle, J Laverty
Journal: BMJ (1993)

Why then is the rate of circumcision up to six times greater than the incidence of preputial disease?Analysis of the clinical findings in children referred for circumcision reported in this week's journal suggests a difference in interpretation of symptoms and clinical signs between surgeons and general practitioners (p 28)."Clearly confusion still exists about what constitutes "pathological" phimosis as distinct from "physiological" non-retractile foreskin.Most cases of pathological phimosis result from balanitis xerotica obliterans, while the remainder may be due to a different, distinct fibrotic disease.'2The underlying difficulty is the imprecision of the term phimosis.An important consideration is that balanitis xerotica obliterans usually develops after the age of 5 years.3'°T he rarity of pathological phimosis under the age of 5 is an important observation since most circumcisions are per- formed before this age.'00ster wrote in the introduction to his paper2 that the publication of Gairdner's article nearly 20 years earlier seemed to have made no significant impression on clinical practice.'Regrettably it seems that the same can be said more than 20 years after 0ster's paper was published.A better understanding of the normal physiology, developmental anatomy, and pathology of the prepuce could prevent the removal of thousands of normal foreskins over the next 20 years.
Audit of major colorectal and biliary surgery to reduce rates of wound infection.
Authors: B D Hancock
Journal: BMJ (1990)

OBJECTIVE--To reduce the rates of wound infection for major colorectal and biliary surgery. DESIGN--Prospective audit of antibiotic prophylaxis by keeping copies of typed notes of operations and annotating them at discharge and at first follow up visit and annual review of prophylactic regimen according to yearly rate of wound infection and modification if necessary. SETTING--The work of one consultant surgeon working in a district general hospital. PATIENTS--All patients having major colorectal resection during 1976-89 (400) and cholecystectomy during 1981-9 (500). MAIN OUTCOME MEASURES--Wound infection, defined as any discharge from the wound as detected by observation during inpatient stay and by specific questioning at the first follow up visit six weeks later. RESULTS--Serial changes in prophylaxis for colorectal surgery resulted in a progressive reduction in the rate of wound infection from 43% in 1976, with no prophylaxis, to 1% during 1986-9 with single intravenous doses of metronidazole and cefuroxime intraoperatively and with lavage of the peritoneal cavity and wound with 0.1% tetracycline. During 1981-7, with no prophylaxis, the rate of infection in biliary surgery was 12% whereas in 1988-9, after the introduction of lavage with tetracycline alone, the rate was reduced to 2%. IMPLICATIONS AND ACTION--Simple prospective audit identified the need for changes in antibiotic prophylaxis; successive rounds of audit resulted in improved rates of wound infection, and lavage with 0.1% tetracycline seemed to be a major factor in achieving this.
STUDIES ON EXPERIMENTAL PNEUMONIA
Authors: Russell L. Cecil, Francis G. Blake
Journal: The Journal of Experimental Medicine (1920)

1. In experimental Pneumococcus Type I pneumonia in monkeys the intravenous injection of Type I antipneumococcus serum exercises a specific therapeutic effect, frees the blood promptly and permanently from pneumococci, shortens the course of the disease, and greatly moderates its severity. Of five monkeys inoculated intratracheally with lethal doses of Pneumococcus Type I, all developed pneumonia, and all recovered following the administration of Type I antipneumococcus serum, while the controls died. 2. The earlier the serum is administered the shorter and less severe the pneumonia. Frequent injections are also an important factor in obtaining favorable results. When serum treatment is instituted late in the disease, the injections must usually be continued over a longer period of time in order to achieve success. 3. Normal horse serum exerts no beneficial effect whatever in experimental Pneumococcus Type I pneumonia.
National Health Information Privacy
Authors: Lawrence O. Gostin
Journal: JAMA (2001)

Health information privacy is important in US society, but existing federal and state law does not offer adequate protection. The Department of Health and Human Services, under powers granted by the Health Insurance Portability and Accountability Act of 1996, recently issued a final rule providing systematic, nationwide health information privacy protection. The rule is extensive in its scope, applying to health plans, health care clearinghouses, and health care providers (hospitals, clinics, and health departments) who conduct financial transactions electronically ("covered entities"). The rule applies to personally identifiable information in any form, whether communicated electronically, on paper, or orally. The rule does not preempt state law that affords more stringent privacy protection; thus, the health care industry will have to comply with multiple layers of federal and state law. The rule affords patients rights to education about privacy safeguards, access to their medical records, and a process for correction of records. It also requires the patient's permission for disclosures of personal information. While privacy is an important value, it may conflict with public responsibilities to use data for social goods. The rule has special provisions for disclosure of health information for research, public health, law enforcement, and commercial marketing. The privacy debate will continue in Congress and within the president's administration. The primary focus will be on the costs and burdens on health care providers, the ability of health care professionals to use and share full medical information when treating patients, the provision of patient care in a timely and efficient manner, and parents' access to information about the health of their children.
Elongation Factor 1-Alpha Sequences Do Not Support an Early Divergence of the Acoela
Authors: Cédric Berney, Jan Pawlowski, Louisette Zaninetti
Journal: Molecular Biology and Evolution (2000)

The phylogenetic position of the Acoela is a key problem in the understanding of metazoan evolution. Recent studies based on 18S ribosomal DNA (rDNA) sequences have placed the Acoela in an extremely basal position as the sister group to all other extant triploblastic animals, suggesting that the phylum Platyhelminthes is polyphyletic. In order to test the results obtained with 18S rDNA, we sequenced elongation factor 1-alpha (EF1a) for the acoel Convoluta roscoffensis and five species of Turbellaria (two polyclads, Leptoplana tremellaris, and Prostheceraeus vittatus, and three triclads, Crenobia alpina, Schmidtea polychroa, and Girardia tigrina). Phylogenetic analyses of EF1a sequences show that the acoel sequences branch within the Platyhelminthes, in opposition to the 18S rDNA data. Moreover, comparison of the central variable region of EF1a shows similar sequence signatures between C. roscoffensis and the three triclad species. Although EF1a sequences fail to prove the monophyly of the phylum Platyhelminthes, they do not confirm the early divergence of the Acoela.
FK506 increases pigmentation and migration of human melanocytes
Authors: H.Y. Kang, Y.M. Choi
Journal: British Journal of Dermatology (2006)

Topical tacrolimus (FK506) is a potential therapeutic option for vitiligo management. Despite its clinical efficacy, the underlying mechanism of how topical tacrolimus induces repigmentation in vitiligo has scarcely been investigated.To investigate the direct effects of FK506 on pigmentation and migration of human melanocytes.Cell proliferation was measured using a Coulter counter. The effects on pigmentation were investigated by measuring melanin contents, tyrosinase activity and tyrosinase expression. To determine the effects of FK506 on cell migration, we performed scratch assays and Boyden chamber assays.FK506 treatment increased melanin contents, although there was an inhibitory effect on growth of melanocytes. The increase of pigmentation was due to the result of the stimulatory action of FK506 on tyrosinase activity and its expression, which eventually led to melanin biosynthesis. Furthermore, cell migration was enhanced by FK506 treatment.These findings provide in vitro evidence demonstrating direct effects of FK506 on pigmentation and melanocyte migration and may provide a possible mechanism for the effect of tacrolimus in vitiligo.
Natural History of Cystic Disease of Breast Treated Conservatively
Authors: D. H. Patey, A. W. Nurick
Journal: BMJ (1953)

Bowurw. 15 another example of high antibody content of foetal blood, and in this respect confirms the previous findings.A strik- ing feature of the results is the consistent relationship between the mother's and the infant's antibody level as well as the magnitude of the latter.The significance of these findings, and the revised view of placental permeability to antibodies to which they lead, was discussed in a previous paper (Calman and Murray, 1951).In that paper we concluded that the simple filtration hypothesis was becoming untenable, and our present results support that opinion. SummaryIn 46 cases the anti-streptolysin 0 titre of the maternal and cord blood was estimated at the time of delivery.The level in the cord was at least twice that of the mother's in 33 cases; it was higher in 41 cases, about the same in three, and lower in only one.In one case both levels were too low to be measured.The material for investigation was obtained through the co- operation of the obstetricians, paediatricians, and labour ward staff of Queen Charlotte's Maternity Hospital.
Out of hours GPs' "culture of avoiding blame" is putting patients at risk
Authors: H. Mooney
Journal: BMJ (2011)

Out of hours GPs are afraid to admit mistakes and use the systems that have been designed to avoid a repeat of incidents because they fear they will be blamed when things go wrong, according to a new report by the NHS Alliance.

The report follows a review of the work of 10 out of hours providers over the past year. It found that a “blame culture” and the “lack of a system that allows people to share information,” were putting patients in danger.

The alliance is now in the process of developing a new anonymised system for …
Pet-Associated Illness
Authors: Diane L. Elliot, Susan W. Tolle, Linn Goldberg, James B. Miller
Journal: New England Journal of Medicine (1985)

AN estimated 55 million dogs and nearly as many cats are kept as pets in the United States.1 Although over 30 human illnesses can be acquired from pets,2 owners are often poorly informed about measures that prevent acquisition of these conditions.3 Despite the frequency of contact between pet and owner, most pet-associated illnesses are infrequent, and health care providers may not be aware of their patterns of transmission or of preventive measures. The topic of pathogens that are transmitted from animals to human beings (zoonoses) has received brief editorial attention recently.4 , 5 In this article, we review in more detail the . . .
Decreased Growth of Established Human Prostate LNCaP Tumors in Nude Mice Fed a Low-Fat Diet
Authors: Yu Wang, John G. Corr, Howard T. Thaler, Yue Tao, William R. Fair, Warren D. W. Heston
Journal: JNCI Journal of the National Cancer Institute (1995)

Geographic variation in the incidence of clinically detected prostate cancer is considerable, with a 120-fold greater incidence in the United States than in China. The incidence of latent prostate cancer, however, shows little variation worldwide, with approximately 30% of men older than age 50 years having microfocal disease (determined by autopsy). Some epidemiologic studies have suggested that a high intake of dietary fat may constitute a risk factor for the development of advanced prostate cancer.We studied the influence of dietary fat content on the growth of tumors established in athymic nude mice with androgen-sensitive, human prostatic adenocarcinoma cells (LNCaP cells). We also investigated whether manipulation of dietary fat content altered prostate-specific antigen (PSA) production by these tumors.Tumors were induced in nude mice by subcutaneous injection of 10(6) LNCaP cells. Both the American Type Culture Collection (ATCC) LNCaP cell line and a more androgen-responsive subline derived from it (i.e., the Harris LNCaP cell line) were used. Mice were fed a 40.5-kcal% fat diet at the time of tumor cell injection. Three weeks later, after measurable tumors were formed, the animals were assigned to receive diets with one of the following fat contents: 40.5, 30.8, 21.2, 11.6, or 2.3 kcal% fat. Food intake, animal weights, and tumor volumes were recorded weekly; serum PSA and testosterone levels were measured at the termination of the study. Post hoc multiple comparisons were made using the Student-Newman-Keuls procedure. Two-sided tests of statistical significance were used to evaluate pairwise comparisons.Tumor growth rates, final tumor weights, and ratios of final tumor weights to animal weights were substantially greater in groups that continued to receive a 40.5-kcal% fat diet than in groups whose diets were changed to 2.3 kcal%, 11.6 kcal%, or 21.2 kcal% fat (all P values < .04). Comparison of these parameters among the 2.3-kcal%, 11.6-kcal%, and 21.2-kcal% dietary fat groups did not reveal any statistically significant differences. No statistically significant differences were noted in total ingested calories, animal weight gain, serum testosterone levels, or histopathologic characteristics of the tumors among the tested dietary groups. Serum PSA levels were highest in the 40.5-kcal% fat group and lowest in the 2.3-kcal% fat group (evaluated only for ATCC LNCaP cells; P < .05).Reduction of dietary fat substantially slows the growth of tumors established from human prostatic adenocarcinoma cells in a murine xenograft model. A positive association persists between tumor volumes and serum PSA levels even after extreme modification of dietary fat content.
Book Review Inborn Metabolic Diseases: Diagnosis and Treatment Third edition. Edited by J. Fernandes, J.-M. Saudubray, and G. Van den Berghe. 467 pp., illustrated. New York, Springer-Verlag, 2000. $119. 3-540-65626-X Metabolic Diseases: Foundations of Clinical Management, Genetics, and Pathology By Enid Gilbert-Barness and Lewis A. Barness. 930 pp. in two volumes, illustrated. Natick, Mass., Eaton, 2000. $279. 1-881299-11-2
Authors: Bridget Wilcken
Journal: New England Journal of Medicine (2001)
Requirement for binding of catalytically active factor VIIa in tissue factor-dependent experimental metastasis.
Authors: B M Mueller, W Ruf
Journal: Journal of Clinical Investigation (1998)

Tissue factor (TF), the initiating cell surface receptor of the coagulation cascade, plays important roles in embryogenesis, angiogenesis, and tumor cell metastasis. It is controversial whether proteolytic function of TF complexed with its serine protease ligand VIIa is required for metastatic tumor dissemination. We show here in a model for TF-dependent experimental hematogenous metastasis, that TF supports metastasis by both proteolytic activity of the TF-VIIa complex and currently undefined functions of the cytoplasmic domain. We demonstrate that ligand binding of VIIa to TF is required for metastasis. Antimetastatic properties of covalently inactivated VIIa provide evidence that ligand binding is insufficient per se to support metastasis, emphasizing that proteolytic activity is necessary for the metastatic process. Ala or Asp mutations of cytoplasmic serine residues were introduced to preclude or mimic phosphorylation. In vivo analysis of these mutants suggests that local protease generation on the tumor cell surface does not serve simply to activate the cytoplasmic domain of TF by serine phosphorylation. Thus, extracellular functions of the catalytically active TF-VIIa complex cooperate with specific functions of the TF cytoplasmic domain to support the complex process of hematogenous tumor cell dissemination.
Impotence: treatment by autoinjection of vasoactive drugs.
Authors: G Williams, M J Mulcahy, E A Kiely
Journal: BMJ (1987)

One hundred and twenty five men with psychogenic or organic impotence used autoinjection of the penile corpora cavernosa with either papaverine or papaverine and phentolamine for a mean period of 10.5 months (range 1-24 months) to achieve penile erection for sexual intercourse. Prolonged (over four hours) painless erection resulted from 34 of the 3513 self administered injections. This seems to be a highly effective approach to treating impotence irrespective of the aetiology.