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Biomedical subjects

L Holloway

Publications and source records attributed to L Holloway.

14 recordsLinked to original sources

The prognosis of adenosquamous carcinomas of the uterine cervix.

OBJECTIVES: Firstly, to identify a cohort of women with invasive adenosquamous carcinomas of the uterine cervix, including mucin-producing squamous cell carcinomas. Secondly, to compare the biological characteristics and behaviour of a cohort of adenosquamous carcinomas with a cohort of non-mucin-producing squamous cell carcinomas. DESIGN: Histological review, retrospective survival analysis. SETTING: Regional multidisciplinary gynaecological oncology service. SUBJECTS: 161 cases of stage 1B and above invasive cervical carcinoma presenting between 1 January 1980 and 31 July 1987. Thirty nine women with adenosquamous carcinomas were compared with 103 women with non-mucin-producing squamous cell tumours. RESULTS: Inclusion of routine stains for mucin in the assessment of histological material resulted in the reclassification of 38 (24%) of the cases, including the identification of 31 mucin-producing squamous cell carcinomas. The survival with adenosquamous tumours was significantly worse than with squamous cell cancers (P = 0.006), 5-year survival rates being 52% and 75% respectively. Multivariate analysis showed that this effect was explained by differences in clinical stage, pelvic lymph node metastasis and vascular invasion by tumour. CONCLUSIONS: The application of routine mucin stains to cervical tumours identifies a group of previously unrecognized adenosquamous cancers. Tumours so identified are likely to pursue a more aggressive clinical course associated with a poorer survival when compared to non-mucin-producing squamous carcinomas.

Adenocarcinoma

Atmospheric sun protection factor on clear days: its observed dependence on solar zenith angle and its relevance to the shadow rule for sun protection.

Global irradiances measured in seven 5-nm bands of UV-B at Rockville, MD (39.1 degrees N, 77.1 degrees W) on 28 clear days near the summer solstice are convoluted with the erythemal action spectrum of human skin to determine dose rates at various hours of the day. These rates are averaged with respect to solar zenith angle to obtain the diurnal variation of mean dose rate and of the Sun Protection Factor (SPF) of the atmosphere (reciprocal of the normalized atmospheric transmissivity) on a typical clear summer day in Rockville. At a 45 degrees zenith angle the atmospheric SPF is computed to be 2.7 and increases rapidly to greater than 7 at 60 degrees. Dose rates are integrated with respect to time to obtain estimates of mean doses for various periods during clear days at Rockville in mid summer and near the autumnal equinox. In mid summer the effective erythemal UV-B exposure during the period when the solar zenith angle is less than 45 degrees is about five times greater than that during the remainder of the day. These observations provide scientific basis for a shadow rule for solar UV-B protection: when shadows are shorter than objects casting them, sunburn is much more likely than at other times.

Humans

Effects of conjugated estrogen on the calcitriol response to parathyroid hormone in postmenopausal women.

We evaluated the effects of estrogen on the calcitriol response to the active peptide, human PTH(1-34), in postmenopausal women. Fifteen women were studied before and again after at least 1 month of treatment with conjugated equine estrogens, 1.25 mg/day. Six women received two series of four graded peptide infusions, each with the sequence 200, 400, 800, and 1600 USP U hPTH(1-34). Nine women received only one dose of peptide, either 200 or 800 U, before and while taking estrogen. Baseline values and the incremental and percent changes in circulating calcitriol 24 h after the 20-min infusions were evaluated. Estrogen treatment resulted in significant reductions in blood levels of calcium (2.26 +/- 0.03 mmol/L vs. 2.16 +/- 0.02, P less than 0.05) and phosphorus (1.23 +/- .05 mmol/L vs. 1.14 +/- 0.03, P less than 0.005), a rise in serum calcitriol concentrations (42.2 +/- 3.9 pg/mL vs. 28.6 +/- 3.1, P less than 0.005), and no change in circulating PTH. The rise in calcitriol after 200 U hPTH(1-34) was significantly greater on estrogen (17.6 +/- 2.0 pg/mL vs. 9.5 +/- 1.8, P less than 0.01), but estrogen did not alter incremental responses to larger doses. When results were normalized for differences in baseline values, the estrogen-related change in response to 200 U was no longer significant. hPTH(1-34) acutely increased urinary clearance of cAMP and phosphorus, but estrogen did not affect this response. We conclude that exogenous estrogen does not increase renal sensitivity to PTH in postmenopausal women.

Calcitriol

Effects of aluminum hydroxide on the parathyroid-vitamin D axis of postmenopausal women.

In previous studies we proposed that estrogen increases circulating calcitriol in postmenopausal women by reducing plasma phosphorus concentrations. For this model to be plausible, a reduction in plasma phosphorus must be itself be sufficient to increase circulating calcitriol in elderly women. To assess this question we studied the effects of Al(OH)3 on daylong circulating levels of phosphorus, calcium, PTH, and calcitriol in 14 postmenopausal women. Subjects were studied on two 7-day periods of dietary control, in which calculated intakes for phosphorus, calcium, and sodium were 950, 800, and 3000 mg/day, respectively. During one randomly assigned period, subjects were given Al(OH)3 with each meal. Al(OH)3 significantly lowered daylong plasma phosphorus concentrations by 17% (0.95 +/- 0.02 mmol/L vs. 1.15 +/- 0.02, P less than 0.0005) (2.94 +/- 0.06 mg/dL vs. 3.57 +/- 0.07), and this was associated with a 38% rise in circulating calcitriol from 61.8 +/- 10.3 pmol/L to 85.2 +/- 10.1 pmol/L (25.7 +/- 4.3 pg/ml to 35.5 +/- 4.2 pg/ml) (P less than 0.0001). The rise in calcitriol correlated significantly with the reduction in phosphorus (r = 0.51, P = 0.03). Al(OH)3 did not significantly alter average daily circulating total calcium (2.32 +/- 0.008 vs. 2.32 +/- 0.005 mmol/L) (9.31 +/- 0.03 vs. 9.29 +/- 0.02 mg/dL), ionized calcium (1.19 +/- 0.003 vs. 1.19 +/- .004 mmol/L), or intact PTH (24.6 +/- 0.6 vs. 24.2 +/- 0.8 ng/L). Moreover, neither the renal phosphorus reabsorption maximum (TmP/GFR), baseline excretion of cAMP, nor the phosphaturic, cAMP, or calcitriol responses to infused hPTH(1-34) were altered by Al(OH)3. We conclude that Al(OH)3 treatment of older women lowers plasma phosphorus concentrations by restricting intestinal phosphorus absorption, and that older women retain the capacity to increase calcitriol levels in response to phosphorus restriction.

Aged

Effects of estrogen on daylong circulating calcium, phosphorus, 1,25-dihydroxyvitamin D, and parathyroid hormone in postmenopausal women.

We studied the effects of estrogen on daylong circulating levels of calcium, inorganic phosphorus, parathyroid hormone (PTH), and 1,25-(OH)2D3 (calcitriol) in a group of 10 postmenopausal women (68.5 +/- 1.4 years, mean +/- SEM). The study was conducted under strict dietary control, with mean calcium and phosphorus intakes of 845 and 970 mg. After treatment with conjugated equine estrogens, 1.25 mg/day, for 1 month, significant decreases in fasting (0800 h) serum levels were observed for calcium (9.09 +/- 0.08 versus 9.46 +/- 0.10 mg/dl, p less than 0.01) and phosphorus (3.38 +/- 0.10 versus 3.73 +/- 0.08 mg/dl, p less than 0.01). On the 0800 h fasting specimen, midmolecule PTH concentrations were higher (44.0 +/- 7.9 versus 34 +/- 8.2 pg/ml, p less than 0.05), but intact PTH was unchanged (28.6 +/- 2.7 versus 29.1 +/- 1.7 pg/ml) and a rise in circulating calcitriol (39.8 +/- 4.3 versus 31.6 +/- 2.1 pg/ml) was marginally significant (p = 0.07). When data represented multiple samples averaged over 7 and 15 h, significant estrogen-related reductions in serum calcium and phosphorus concentrations were observed. In addition, estrogen was associated with a significant rise in the daylong (15 h) level of calcitriol (39.4 +/- 4 versus 30.5 +/- 2.4 pg/ml, p less than 0.01). Daylong mid- and intact PTH concentrations were unchanged on estrogen compared to baseline values. No significant correlations were observed between changes in fasting calcitriol level and changes in fasting concentrations of calcium, phosphorus, or PTH. Further, the rise in daylong calcitriol concentration did not correlate significantly with changes in fasting or integrated values of calcium or PTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Effects of short term administration of recombinant human growth hormone to elderly people.

We evaluated the effects of recombinant human GH (rhGH) in 16 men and women more than 60 yr of age. After 10 days of dietary equilibration and control collections, subjects were randomly assigned to receive 0.03, 0.06, or 0.12 mg/kg rhGH by daily injection for 7 days. A brisk rise in circulating somatomedin-C (insulin-like growth factor-I) occurred in all subjects, and this rise was dose dependent. rhGH produced striking changes in nitrogen retention, sodium excretion, and the parathyroid-vitamin D axis. Twenty-four-hour urinary nitrogen excretion decreased from 8.00 +/- 0.33 to 5.01 +/- 0.33 g (P less than 0.001), and sodium excretion decreased from 45.9 +/- 2.96 to 21.2 +/- 3.48 mmol/day (P less than 0.001). Serum calcium concentrations did not change, but serum inorganic phosphorus levels of 1.08 +/- 0.04 mmol/L at baseline increased significantly after rhGH treatment to 1.33 +/- 0.04 mmol/L (P less than 0.001). Increases were also observed in circulating PTH (53.2 +/- 6 vs. 39.5 +/- 4.2 ng/L; P less than 0.01) and calcitriol (82.8 vs. 65.8 pmol/L; P less than 0.05). A rise in serum osteocalcin (10.3 +/- .86 vs. 8.0 +/- 0.5 micrograms/L; P less than 0.05) was accompanied by increased urinary excretion of hydroxyproline (628 +/- 63 vs. 406 +/- 44 mumol/day; P less than 0.01). Despite the reduction in sodium excretion, marked increases were observed in urinary calcium (6.04 +/- 0.97 vs. 3.27 +/- 0.40 mmol/day; P less than 0.01). rhGH significantly impaired oral glucose tolerance and reduced insulin sensitivity, but was otherwise well tolerated and produced no systematic changes in weight or blood pressure. The results of this study indicate that rhGH requires further study as a potential agent for attenuating or reversing the loss of muscle and bone in elderly people.

Age Factors

Bronchial gland duct ectasia in fatal bronchial asthma: association with interstitial emphysema.

To determine the incidence of bronchial gland duct ectasia in fatal asthma and its association with interstitial emphysema, the histological features of 72 patients in whom death was considered to be due to asthma, and 72 matched control subjects in whom sudden death was not attributed to asthma, were reviewed. In all cases and controls, sections of two or more blocks of lung tissue stained with haematoxylin and eosin were obtained at necropsy. Bronchial gland duct ectasia was diagnosed if there was more than one abnormally dilated epithelial lined protrusion from a bronchus, extending through the smooth muscle layer. A histological diagnosis of asthma was made if four of the five following criteria were present: mucus plugging, basement membrane thickening, epithelial shedding, submucosal eosinophil leucocyte infiltration and smooth muscle hypertrophy. A histological diagnosis of asthma was made in 53 of 72 clinical cases of fatal asthma and in five of 72 control subjects. Interstitial emphysema was present in 10 clinical cases of fatal asthma, all of whom had bronchial gland duct ectasia and a histological diagnosis of asthma. Interstitial emphysema was not observed in control subjects. It is concluded that bronchial gland duct ectasia is a common histological feature of severe asthma, and that interstitial emphysema may be consequent on rupture of these dilated gland ducts.

Asthma

Familial distal dysautonomia.

A patient is described who presented with painful feet on exercise. He had no evidence of peripheral vascular disease but did have anhidrosis and failure of vasodilatation in the hands and feet suggesting peripheral dysautonomia. Examination of his mother and a cousin and clinical histories of blood relatives suggested that his problem was a severe presentation of a familial distal dysautonomia. In other family members this was represented by dry hands and feet and variable vasomotor symptoms. This condition appeared to be autosomal dominant.

Adult

Management of Pneumocystis carinii pneumonia in the immunocompromised host.

From 1982 to 1987, 22 patients with proven Pneumocystis carinii pneumonia were diagnosed at Wellington Hospital. Patients comprised 15 males and 7 females aged 15-76 years and included seven with AIDS, eight with haematological malignancy and seven with renal disease. Two distinct clinical prodromes occurred. In renal patients a classic fulminating pneumonitis developed over 24 to 72 hours. In patients with AIDS a more indolent illness occurred lasting 3 or more weeks and was characterised by fever, dry cough and breathlessness. Haematology patients showed no specific duration of prodrome. At the time of diagnosis all had an abnormal chest radiograph and the arterial PO2 was reduced in all but one case. An invasive diagnostic procedure was performed in all except one case where the diagnosis was made at post mortem. Two patients required a second procedure to establish the diagnosis. Procedures performed included bronchoalveolar lavage [14], open lung biopsy [7] and transbronchial lung biopsy [2]. All patients were treated with high dose cotrimoxazole and 18 survived to leave hospital. A review of the approach to the diagnosis and treatment of Pneumocystis carinii pneumonia is presented.

Acquired Immunodeficiency Syndrome

Prognostic significance of tumor grade in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis.

The prognostic significance of histologic tumor grade has been evaluated in 1537 women entered into the Ludwig Trials I-IV of adjuvant therapy for node-positive breast cancer. Tumor grade was determined on histologic review of primary tumor sections by two central review pathologists using a modification of the Bloom and Richardson grading system. The 5-year overall survival rates (+/- SE) were: Grade 1, 86% +/- 2; Grade 2, 70% +/- 2; and Grade 3, 57% +/- 2 (P less than 0.0001). This survival difference was seen in both premenopausal (P less than 0.0001) and postmenopausal (P less than 0.0001) women. Significant differences in disease-free survival (DFS) by tumor grade were also observed (P less than 0.0001). The tumor grade determined by the 75 contributing local clinic pathologists was also highly significant for predicting DFS and overall survival. Tumor grade remained a statistically significant prognostic factor for DFS (P less than 0.0001) and overall survival (P less than 0.0001) in multivariate analyses controlling for nodal status, tumor size, estrogen receptor status, menopausal status, age, peritumoral vessel invasion, and treatment assigned. In postmenopausal patients for whom adjuvant treatment was compared with no adjuvant therapy, the prognostic significance of tumor grade was modified by the effect of treatment. The presence of vessel invasion by primary tumor cells was a stronger predictor of early recurrence than was increasing tumor grade in postmenopausal patients who received no adjuvant therapy. The higher failure rates for patients with high-grade tumors was due to a larger number of failures in regional and visceral sites. Tumor grade can be determined by any pathologist and allows for selection of a subpopulation of breast cancer patients at high risk for early mortality.

Adult