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Biomedical subjects

E Robinson

Publications and source records attributed to E Robinson.

At least 91 records · Page 5Linked to original sources

Living with mastectomy and breast conservation treatment: who suffers more?

Sixty-five patients who underwent modified radical mastectomy were compared with 55 breast conservation patients, all of whom were in stage I, II or III of breast cancer and were under treatment at an oncology clinic in northern Israel. The main findings indicate no differences between the groups in physical, psychosocial, marital or medical interaction, according to the CARE scale. These findings reflect the results of similar comparative studies conducted during the 1980s and 1990s as documented in the literature. Sexual interaction showed statistical differences favoring the women who had undergone mastectomies.

Adult↗

The novel anticonvulsant, gabapentin, protects against both convulsant and anxiogenic aspects of the ethanol withdrawal syndrome.

The effects of the anticonvulsant, gabapentin, were investigated, in mice, on the withdrawal convulsive behaviour and anxiety-related behaviour that are produced by cessation of prolonged intake of ethanol. When given at 50 or 100 mg/kg, this compound decreased the rise in handling-induced hyperexcitability which occurs during the withdrawal period; the effects were most pronounced for the first 4 hr after administration. Gabapentin also decreased the convulsive response to an audiogenic stimulus during the withdrawal period. The elevated plus-maze, with both traditional and ethological indices of activity was used as a test of anxiety-related behaviour after cessation of chronic ethanol treatment. Gabapentin, at 50 and 100 mg/kg, was found to decrease some, although not all, of the signs of withdrawal-induced anxiety. At doses up to and including 200 mg/kg, gabapentin had no effect on motor co-ordination or spontaneous locomotor activity in control animals. The results demonstrated that gabapentin has a selective action in decreasing both convulsive and anxiety-related aspects of withdrawal behaviour after chronic ethanol treatment. It is possible that further studies with this compound may shed further light on the mechanisms involved in the withdrawal syndrome.

Acetates↗

Short-term antihypertensive medication does not exacerbate sleep-disordered breathing in newly diagnosed hypertensive patients.

It has been speculated for some time that various antihypertensive medications may have a deleterious effect on respiration during sleep and thereby enhance the apparent association between hypertension and sleep apnea/hypopnea (SAH). However, there are few data to support this contention. The present study used a double-blind, randomized, cross-over design to contrast the effects of 6 weeks treatment with alpha-methyldopa and the combination of hydrochlorothiazide and amiloride with that of amlodipine and the combined diuretics in a group of 24 newly diagnosed patients with primary hypertension. All-night polysomnography was performed before the initiation of therapy (baseline) and at the end of the two treatment periods. Respiratory variables failed to reveal any significant differences between the treatments and baseline, or between the two different treatment regimens. The two treatment regimens achieved similar reductions in blood pressure. The prevalence of SAH was 25% before treatment, which is comparable to a prevalence of 20% in a similar group drawn from the same population but receiving various antihypertensive medications. The findings of this study are in agreement with previous reports using other classes of antihypertensive drugs that also failed to detect any tendency for increases in nocturnal respiratory disturbance indices over assessment periods of 8 weeks or shorter.

Amlodipine↗

Intensive chemotherapy using cisplatin and fluorouracil followed by radiotherapy in advanced head and neck cancer.

This protocol was designed to achieve an improvement in the overall and disease-free survival in locally advanced, previously untreated carcinoma of the head and neck. 53 patients (pts) with locally advanced Stages III and IV, MO squamous cell carcinoma of the nasopharynx, larynx, paranasal sinuses, oral cavity, oropharynx, hypopharynx and one of unknown origin were treated with intensive chemotherapy followed shortly thereafter by radiotherapy. Induction chemotherapy consisted of two cycles of cisplatin 100 mg/m2 over 60 min on day 1, plus 5FU 1000 mg/m2 continuous infusion over 24 h on days 2-5, with a 10-day interval between the two cycles, followed by definitive radiotherapy after 10 days. The overall response rate to chemotherapy was 79%, with a 28% complete response (CR) rate and a 51% partial response (PR) rate. The overall CR rate after radiotherapy was 70%. With a median follow-up period of 48 months, the 5-year actuarial survival and disease-free survival rates were 67% and 45%, respectively. No difference was found in the survival probability of pts with carcinoma of the nasopharynx, larynx or other primary sites. The survival of pts with a performance status (PS) < or = 1 was better than pts with PS > 1, 72% versus 51% (not significant). The survival probability of complete responders to chemotherapy was superior than the survival of non-complete responders to chemotherapy, 100% versus 54% [P = 0.001]. The main toxicity was mucositis during radiotherapy. In conclusion, this treatment regimen demonstrated a high CR rate and survival probability in pts with locally advanced and mostly inoperable head and neck cancer.

Adolescent↗

The immunogenicity of Haemophilus influenzae: meningococcal protein conjugate vaccine in Polynesian and non-Polynesian New Zealand infants.

OBJECTIVE: To examine the comparative immunogenicity of the Haemophilus influenzae type b-meningococcal protein (PRP-OMP) conjugate vaccine in Polynesian and non-Polynesian New Zealand infants. METHODOLOGY: Fifty-six Polynesian and 53 non-Polynesian infants aged 2-7 months recruited from primary health care settings in Auckland received a two-dose primary series of PRP-OMP. A sub-sample of 83 participants received a booster dose of PRP-OMP at 12-16 months of age. Anti-PRP antibody concentrations were measured in pre- and post-vaccination blood samples. RESULTS: Antibody responses consistent with long-term protection (> or = 1.00 microgram/mL) were observed in 72, 85 and 95% of children following the first, second and booster doses. CONCLUSIONS: Despite differences in disease epidemiology, PRP-OMP was highly immunogenic in Polynesian and non-Polynesian infants.

Antibody Formation↗

Prostate cancer mortality in New Zealand: the past and projections for the future.

BACKGROUND: Ageing male populations and improved diagnosis of early stage disease have contributed to the increasing incidence of prostate cancer observed in many Western countries. The clinical significance of these diagnosed cancers is, however, currently unclear. The aim of this study is to examine trends over time in prostate cancer mortality as an indicative measure of clinically significant disease during a 29-year period (1965-93) which preceded the extensive use of early cancer diagnostic techniques or radical therapy protocols. METHODS: Age-specific and age-standardized rates were calculated for each year during the study period, using routinely collected mortality and demographic data. A Poisson regression model was used to describe trends in the age-specific rates over time to predict numbers of prostate cancer deaths and the lifetime risk of death over the next 20 years. RESULTS: Significant annual increases ranging from 1 to 2.6% were found for age-specific prostate cancer mortality rates over the 29-year time period, with the largest increases experienced in the younger age groups at risk. Based on projected population ageing and growth alone, annual numbers of prostate cancer deaths are predicted to increase from 487 in 1993 to 664 by the year 2006 and then to 833 by the year 2016. Continuation of the observed increases in age-specific mortality rates would result in a predicted 797 deaths by the year 2006, while an expected 1115 deaths is calculated for the year 2016. This would correspond with an increase in the lifetime risk of death from prostate cancer from a present 3.7 to 4.5% in 10 years and 6.2% in 20 years. CONCLUSIONS: The changing pattern of prostate cancer mortality described in this study is likely to represent a significant increase in the incidence of clinically significant disease. This will have a significant impact on the ageing New Zealand male population, and important implications for the provision of effective treatment and preventive strategies.

Age Distribution↗

Circumstances of falls resulting in hip fractures among older people.

OBJECTIVES: To describe the circumstances of falls resulting in hip fractures among older people and to determine whether the circumstances differ by gender, age, and residential status. DESIGN: Cross-sectional study. SETTING: Two hospitals in Auckland, New Zealand, in which all individuals aged 60 years or older with a fracture of the proximal femur are hospitalized. PARTICIPANTS: A total of 911 individuals (97% response rate) were hospitalized with fractures of the proximal femur; 77% were women, 66% were aged 80 years or older, and 58% were living in private homes at the time of fracture. MEASUREMENTS: Data were collected face-to-face by a trained interviewer using a standardized questionnaire. RESULTS: Ninety-six percent of the fractures were associated with a fall, with fewer that 2% of subjects reporting that their fractures occurred spontaneously before a fall. Sixteen percent of fractures were associated with an acute medical or physical condition. Although 85% of the fractures involving a fall occurred at home, only about 25% of these were associated with an environmental hazard, and only a proportion of these were likely to have been amenable to modification. The circumstances of falls differed significantly by age and residential status. CONCLUSION: Strategies aimed at preventing fall-related hip fractures among the old old and among institutionalized individuals should focus primarily on the modification of intrinsic factors. Modification of environmental hazards has the greatest potential for prevention among the young old and those living in private homes.

Accidental Falls↗

Molecular characterization and cellular localization of TpLRR, a processed leucine-rich repeat protein of Treponema pallidum, the syphilis spirochete.

Automated Edman degradation was used to obtain N-terminal and internal amino acid sequences from a 26-kDa protein in isolated Treponema pallidum outer membranes (OMs). The resulting sequences enabled us to PCR amplify from T. pallidum DNA a 275-bp fragment of the corresponding gene. The complete nucleotide sequence of the gene was determined from fragments amplified by long-distance PCR. Primer extension verified the assigned translational start of the open reading frame (ORF) and putative upstream promoter elements. The ORF encoded a highly basic (pI 9.6) 26-kDa protein which contained an N-terminal 25-amino-acid leader peptide terminated by a signal peptidase I cleavage site. The mature protein contained seven tandemly spaced copies (as well as an eighth incomplete copy) of a leucine-rich repeat (LRR), a motif previously identified in a number of prokaryotic and eukaryotic proteins. Accordingly, the polypeptide was designated T. pallidum leucine-rich repeat protein (TpLRR). Although Triton X-114 phase partitioning showed that TpLRR was hydrophilic, cell localization studies showed that most of the antigen was associated with the peptidoglycan-cytoplasmic membrane complex rather than being freely soluble in the periplasmic space. Immunoblot studies showed that syphilis patients develop a weak antibody response to the antigen. Lastly, the lrr(T. pallidum) gene was mapped to a 60-kb SfiI-SpeI fragment of the T. pallidum chromosome which also contains the rrnA and flaA genes. The function(s) of TpLRR is currently unknown; however, protein-protein and/or protein-lipid interactions mediated by its LRR motifs may facilitate interactions between components of the T. pallidum cell envelope.

Amino Acid Sequence↗

Tromp1, a putative rare outer membrane protein, is anchored by an uncleaved signal sequence to the Treponema pallidum cytoplasmic membrane.

Treponema pallidum rare outer membrane protein 1 (Tromp1) has extensive sequence homology with substrate-binding proteins of ATP-binding cassette transporters. Because such proteins typically are periplasmic or cytoplasmic membrane associated, experiments were conducted to clarify Tromp1's physicochemical properties and cellular location in T. pallidum. Comparison of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis mobilities of (i) native Tromp1 and Tromp1 synthesized by coupled in vitro transcription-translation and (ii) native Tromp1 and recombinant Tromp1 lacking the N-terminal signal sequence revealed that the native protein is not processed. Other studies demonstrated that recombinant Tromp1 lacks three basic porin-like properties: (i) the ability to form aqueous channels in liposomes which permit the influx of small hydrophilic solutes, (ii) an extensive beta-sheet secondary structure, and (iii) amphiphilicity. Subsurface localization of native Tromp1 was demonstrated by immunofluorescence analysis of treponemes encapsulated in gel microdroplets, while opsonization assays failed to detect surface-exposed Tromp1. Incubation of motile treponemes with 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)-diazarine, a photoactivatable, lipophilic probe, also did not result in the detection of Tromp1 within the outer membranes of intact treponemes but, instead, resulted in the labeling of a basic 30.5-kDa presumptive outer membrane protein. Finally, analysis of fractionated treponemes revealed that native Tromp1 is associated predominantly with cell cylinders. These findings comprise a body of evidence that Tromp1 actually is anchored by an uncleaved signal sequence to the periplasmic face of the T. pallidum cytoplasmic membrane, where it likely subserves a transport-related function.

Azirines↗

1,25-dihydroxyvitamin D3 regulates estrogen metabolism in cultured keratinocytes.

Local estrogen metabolism may play an important role in modulating cell development in peripheral tissues such as breast, adipose, and bone. C19 androgens are converted to C18 estrogens by the enzyme aromatase, overexpression of which is associated with breast cancer. Interconversion of active estradiol (E2) to inactive estrone is controlled by various isoforms of the enzyme 17beta-hydroxysteroid dehydrogenase (17betaHSD). We have studied the expression of these two enzymes in human keratinocytes and report rapid changes in 17betaHSD activity in response to treatment with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Keratinocytes cultured in serum-free medium showed aromatase activity of 2.5 fmol/h x mg cell protein, which was unaffected by any culture treatment. A much higher level of 17betaHSD activity was observed in the keratinocytes, predominantly conversion of E2 to estrone (approximately 120 pmol/h x mg cell protein). This inactivation of E2 increased in a dose-dependent fashion after treatment of the cells with antiproliferative doses of 1,25-(OH)2D3 (0.1-200 nM). The effect of 1,25-(OH)2D3 on 17betaHSD activity was enhanced by simultaneous treatment with dexamethasone, which also increased the antiproliferative action of 1,25-(OH)2D3. Reverse transcription-PCR and Northern analysis showed that keratinocytes expressed messenger RNA for three 17betaHSD isoenzymes (types I, II, and IV). Treatment with 1,25-(OH)2D3 (10 nM for 20 h) resulted in the up-regulation of messenger RNA levels for type 2 17betaHSD. Further RNA studies combined with E2 binding experiments demonstrated the presence of estrogen receptors in the cultured keratinocytes. These data indicate that keratinocytes are potential targets for systemically or locally produced estrogens, which may, in turn, play a key role in the development of normal skin. In particular, we propose that 17betaHSD isoenzymes are key target genes for 1,25-(OH)2D3 in keratinocytes and may be an important feature of the antipsoriatic effects of vitamin D and its analogs.

Androstenedione↗

Intensive short cause chemotherapy followed by radiotherapy of locally advanced nasopharyngeal carcinoma.

BACKGROUND: We designed a protocol with the goal of improving the disease free and overall survival of patients with previously untreated Stage IV nasopharyngeal carcinoma (NP(C)). The regimen consisted of intensive induction chemotherapy followed shortly thereafter by radiation therapy. METHODS: Between March 1986 and March 1992, 27 patients with T3-4, N2-3, M0 squamous cell carcinoma of the nasopharynx were treated with 2 cycles of chemotherapy, using cisplatin, 100 mg/m2 intravenously, on Day 1, and 5-fluorouracil (5-FU), 1000 mg/m2 per day continuous infusion, on Days 2-5. The second cycle was given on Day 16 and was followed by radiotherapy (RT), 70 Gray, given on Day 31. RESULTS: The objective response rate to chemotherapy was 93%, with a 37% complete response (CR) rate and a 56% partial response (PR) rate. The overall CR rate after RT was 85%. With a median follow-up of 60 months, the overall actuarial survival rate was 66%. Patients who had a CR after chemotherapy had a superior survival probability (100%). Toxicity was tolerable, without lethal complications. CONCLUSIONS: This study demonstrates that cisplatin/5-FU chemotherapy given in an intensive schedule and followed shortly thereafter by radical RT can improve the CR rate and survival of patients with locally advanced NPC, with tolerable toxicity.

Adolescent↗

[Experience with conservative therapy in primary breast cancer: experiences Northern Israel Oncology Center, 1981-1990].

Between 1981 and 1990, 346 patients with primary breast cancer were treated using breast conservation. Mean age was 55 +/- 13 years and median follow-up 53 months. 36.5% were in pathological Stage I, 55% in Stage II, and 4% in Stage III, while 4.5% were in clinical Stages I-II. 60% of the lesions were excised with good margins, 12% with close margins (0.5 cm), 2.5% with macroscopic residuals, 7.5% with microscopic residuals and 18% with margins that could not be determined. Level II lymph node dissection was performed in 334 patients (97%). Adjuvant therapy (combination of chemotherapy and/ or hormones) was given to 223 (64%). Radiotherapy, usually 50-55 Gy tangential photon irradiation to the whole breast, was given to 335 (97%); electron or photon "boost" to the tumor bed was given to 234 (70%); most patients received 20 Gy. Most node-positive patients received 50 Gy to the lymphatic drainage system. A year after completion of radiotherapy cosmetic results were rated as good in 195/212 (92%), moderate in 17/212 (8%), but in none as poor. 5-year actuarial survival was 90% for Stage I and 81% for Stage II disease. 24 (7%) developed breast recurrence, 8 of whom (2%) also had distant metastases; 5 (1.5%) developed supraclavicular lymph node metastases and 59 (17%) distant metastases. Predictors of poor survival or local recurrence were: age under 40 years, premenopausal status, multifocality, and blood/lymph vessel infiltration by tumor cells. The satisfactory level of local control achieved is attributed to the high doses of radiation administered in high-risk lesions (up to 70 Gy total tumor dose).

Actuarial Analysis↗