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Biomedical subjects

R M Clark

Publications and source records attributed to R M Clark.

At least 73 records · Page 4Linked to original sources

A method for separation and quantification of phospholipid classes in human milk.

A simple, isocratic method for separating the major phospholipid classes of human milk by HPLC is described. Resolution of phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylcholine, and spingomyelin from human milk phospholipids was achieved in 30 min on a silica column. Total phospholipids were injected in 50 microliter of chloroform:diethyl ether (1:2, vol/vol) and eluted with a solvent mixture of acetonitrile:methanol:sulfuric acid (100:3:.05, vol/vol/vol) at a flow rate of 2.5 ml/min. Fractions were collected and each phospholipid class quantified by analysis of inorganic phosphorus after sulfuric acid digestion. A repeatability study with 19 samples had a coefficient of variation of 5.3%. The analytical recoveries of phospholipid standards averaged 98%. Recoveries varied with phospholipid class; variation was greatest with spingomyelin.

Chromatography, High Pressure Liquid↗

Macronutrients in human milk at 2, 12, and 16 weeks postpartum.

This study evaluated changes in human milk composition from 2 to 16 weeks postpartum. Milk from 12 mothers was analyzed for lipid (utilizing a modified Folch), lactose (enzymatic hydrolysis), and nitrogen (semi-micro Kjeldahl). Energy was calculated by fractional analysis and bomb calorimetry. All samples were from well-defined subjects, and uniform collection procedures were used. Milk lipid, total nitrogen, and energy content differed significantly from one woman to another. Lipid and energy content increased from 3.98 +/- 1.0 to 5.50 +/- 1.1 gm/100 ml and 68.5 +/- 9.8 to 83.0 +/- 11.1 kcal/100 ml, respectively, and nitrogen content decreased significantly from 0.24 +/- 0.05 to 0.16 +/- 0.02 gm/100 ml from 2 to 16 weeks postpartum. Lactose remained statistically stable, increasing from 6.3 +/- 0.7 to 7.0 +/- 0.7 gm/100 ml. Estimates of energy from fractional analysis of macronutrients produced lower caloric estimates, especially at 2 weeks postpartum. Statistical differences over time and between and among mothers were found at all periods studied; therefore, on the basis of these data, we caution against reliance on single sample values as representative of mature milk either for individuals or for groups.

Energy Intake↗

Growth and phosphorus metabolism in premature infants fed human milk, fortified human milk, or special premature formula. Use of serum procollagen as a marker of growth.

Human milk promotes less than optimal growth and is associated with phosphorus deficiency and decreased bone mineralization in very-low-birth-weight (VLBW) infants. In this study, the effects of feeding premature infants either human milk (HM), fortified human milk (FHM), or special premature formula (Similac Special Care [SSC]) on growth, phosphorus metabolism, and serum type I procollagen (pColl-I-C) were evaluated. Infants fed FHM exhibited a rate of weight gain and an increase in head circumference comparable with infants fed SSC and significantly greater than infants fed HM, despite the fact that both the FHM group and the HM group demonstrated biochemical evidence of phosphorus deficiency. The pColl-I-C concentrations in VLBW infants were tenfold to 20-fold greater than concentrations in normal children older than 2 years of age. The pColl-I-C levels correlated positively with weight gain and were significantly greater in the FHM and SSC groups than in the HM group. By contrast, serum alkaline phosphatase levels did not correlate with weight gain and were significantly lower in the rapidly growing SSC group than in either of the two groups with phosphorus deficiency and presumed poor bone mineralization. We conclude that the serum pColl-I-C concentration is a biochemical marker of growth in VLBW infants and may prove useful as a predictor of growth responses to various nutritional and therapeutic interventions.

Blood Proteins↗

Breast cancer. Experiences with conservation therapy.

A series of 1,504 patients with clinically node-negative carcinoma of the breast treated by breast conservation has been followed for 26 years. The majority did not have an axillary dissection. A relative survival of 84% at 5 years and 72% at 10 years compares favorably with reported survival rates for radical surgery. Postoperative irradiation does not influence survival but breast irradiation reduces relapse in the breast. Irradiation of the regional nodes is unnecessary. Lumpectomy alone in clinically node-negative patients produces a survival rate equivalent to more radical treatment. Younger patients had larger tumors, an increased risk of breast relapse, and reduced survival. Local or distant relapse was not a function of estrogen receptor (ER) or progesterone receptor (PR) status.

Adult↗

Within-day variation of taurine and other nitrogen substances in human milk.

Milk samples were collected from seven mothers during their 8th wk of lactation. On the day of collection one breast was completely emptied at 600, 1000, 1400, 1800, and 2200 h. Concentrations of total nitrogen, protein nitrogen, urea nitrogen, and free amino acids (taurine and glutamine plus glutamic acid) were determined. Concentrations of these nitrogen substances in the milk differed significantly among women but were relatively constant during the day. The mean concentrations of these substances per 100 ml of milk were total nitrogen, .189 g; protein nitrogen, .145 g; urea nitrogen, .020 g; taurine 34.9 mumol; glutamine plus glutamic acid, 200.0 mumol.

Chromatography, High Pressure Liquid↗

Drinking water and cancer mortality.

The problem of understanding the possible adverse health effects of organic chemical contaminants in drinking water is not new, but national concern has intensified in recent years. Despite this concern and regulatory efforts, no definitive relationship has been established between organic contamination and human health effects. This paper examines some of the sources of possible organic contamination, current knowledge concerning human health effects and the most current epidemiological data. Historic CCE and CAE data were extracted from STORET and used in regression analyses. Age-adjusted 20-year average cancer mortality rates were regressed against the sum of CAE and CCE for those counties with STORET monitoring data of their drinking water source. Results indicate statistically highly significant relationships particularly for GI-urinary tract cancers.

Carcinogens↗

Primary lymphoma of the breast.

Primary lymphoma of the breast is a rare entity. This paper adds a further 16 cases to the world literature. Axillary nodal status appears to be an important prognostic factor for survival. Stage IE patients should be treated with an excisional biopsy followed by radiation to the breast and to the regional nodes. Combined treatment with systemic chemotherapy with local irradiation should be considered for patients with Stage IIE disease (breast and axillary nodes).

Adult↗

Within-day variation of lipolytic activity in human milk.

Milk was collected from six mothers during their 8th wk of lactation to determine the diurnal variation of bile salt-stimulated lipase and serum-stimulated lipase. On the day of collection, one breast was completely emptied at 0600, 1000, 1400, 1800, and 2000 h. Activities of bile-stimulated lipase and serum-stimulated lipase in the milk were determined. Activity of bile-stimulated lipase was constant throughout the day, whereas serum-stimulated lipase activity varied significantly with time. Both activities differed significantly in milk from different women. Time of collection must be considered when measuring activity of serum-stimulated lipase but is not a major variable when measuring activity of bile-stimulated lipase in human milk. These results may be helpful when designing future studies involving these enzymes.

Bile Acids and Salts↗

Chronic syndrome of inappropriate antidiuretic hormone secretion and hypertension in a patient with olfactory neuroblastoma. Evidence of ectopic production of arginine vasopressin by the tumor.

A 28-year-old man with the chronic syndrome of Inappropriate antidiuretic hormone secretion and hypertension was found to have an olfactory neuroblastoma. We demonstrated evidence of elevated circulating arginine vasopressin levels, significantly elevated arginine vasopressin and vasopressin neurophysin levels in the tumor extract, and immunohistochemical staining for arginine vasopressin and vasopressin neurophysin in the tumor cells. The patient's clinical syndrome, including hypertension, resolved following subtotal removal of the tumor and radiation therapy. This study identified olfactory neuroblastoma as a definite cause of ectopic arginine vasopressin secretion causing the syndrome of inappropriate antidiuretic hormone secretion.

Adult↗

Radiotherapy alone in breast cancer. I. Analysis of tumor parameters, tumor dose and local control: the experience of the Gustave-Roussy Institute and the Princess Margaret Hospital.

This retrospective study involved 463 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave-Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to tumor response, local recurrence rate, tumor size, tumor fixation, nodal fixation and tumor dose. Conventional statistical analysis of local control showed two significant factors: tumor dose and tumor size. Multivariate analysis permitted to define an "individual risk" (IR) of local recurrence according to three independent factors: tumor size, tumor fixation, and nodal fixation. It was shown that the IR was a good prognostic factor for local control. Increase in tumor dose gave a similar effect in the local recurrence relative risk for all the IR groups. According to the slope of the dose-effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of local recurrence 2-fold. In fact, it was shown that tumor dose was the most significant independent factor on local control, able to produce up to a 10-fold increase compared to 2-fold decrease for tumor size. If the IR of local recurrence is known, a theoretical predictive value on local control, taking into account the tumor dose, can be determined according to the present data.

Breast Neoplasms↗

Internal mammary lymphoscintigraphy in the conservative management of breast carcinoma: an update and recommendations for a new TNM staging.

The results of internal mammary lymphoscintigraphy (IML) in 524 patients with breast carcinoma who underwent partial mastectomy, with or without axillary dissection, demonstrate the predictive value of an abnormal lymphoscintigram. There was a significant difference (P less than 0.0005) in actuarial survival between patients with normal and abnormal IML. In view of the increased mortality associated with metastases to both internal mammary and axillary lymphatics compared with involvement of either site alone, and the most favourable outcome in patients with involvement of neither site, it is proposed that the current TNM staging for breast carcinoma should henceforth include the status of internal mammary lymph nodes determined by radiocolloid lymphoscintigraphy. Further refinement of the N status into NA (axilla) and N1 (internal mammary nodes) is suggested. Stages I, II, and III should designate, respectively, patients with no evidence of involvement of either lymphatic site, patients with involvement of one or the other site and patients with involvement of both sites. This would constitute a more rational approach to the staging and management of the patient with breast carcinoma and would also provide a more accurate means of evaluating the true efficacy of current strategies in comparable groups of patients. Unrecognised internal mammary lymphatic metastases have probably confounded the results of past prospective trials.

Actuarial Analysis↗

Role of radiation therapy in localized non-Hodgkin's lymphoma.

Relapse occurs in 50% of patients receiving radiation for clinical stage (C.S.) I and II nodal and extranodal non-Hodgkin's lymphoma (N.H.L.). Prior to the introduction of intensive chemotherapy those failing primary control with irradiation and most of those who relapsed died of their disease with a resultant overall mortality of 50%. An analysis of Princess Margaret Hospital results with radiation for C.S. I and II N.H.L. between January 1967 and December 1978 revealed that tumour bulk, age, stage and histology were of independent prognostic significance. It was possible to group patients using combinations of these attributes so that each group encompassed only patients with similar outcomes. Such prognostic groups were identified separately within the low grade and the intermediate plus high grade categories of the Working Formulation. Patients with a high probability of cure with radiation were so defined. Also those patients in whom chemotherapy would be optimal initial therapy were also defined. Such patients were in the intermediate plus high grade histology groups. Thirty percent of all patients with low grade histology lymphoma had an actuarial survival of 83%, and relapse-free rate of 63% at 10 years. By implication, approximately 20% of all patients with these histologies seen at the Princess Margaret Hospital for the same time period achieved prolonged relapse-free survival by localized therapy. This is at variance with the implications of staging from studies where laparotomy and multiple bone marrow biopsies have been used. Such aggressive staging procedures suggest truly localised disease in only 5-6% of patients with low grade lymphoma. A significant relationship between radiation dose and disease control was demonstrated only for patients with intermediate and high grade lymphoma of medium or large bulk. A minimum tumour dose of 30 Gy was required for optimal local control with radiation.

Adult↗

Total phospholipid analysis in human milk without acid digestion.

A colorimetric method for measuring the organic phosphorus in human milk without acid digestion was studied. Human milk samples were assayed and compared to phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin standards. Spectral and calibration curves prepared from phospholipid standards were equivalent. Absorption maxima occurred between 720 and 740 nm. A reproducibility study of twenty total lipid samples had a coefficient of variation of 3.8%. Phosphorus ranged from 4.7 to 5.5 micrograms with a mean +/- SD of 5.2 +/- 0.2 micrograms P. The recovery of phosphatidylcholines added to 10 mg samples of human milk triacylglycerols ranged from 99.0 to 102.1%. The results from the new method were comparable to those obtained by a modified Fiske and Subbarow method for measuring inorganic phosphorus after sulfuric acid digestion of the milk lipids. We concluded that the new method provides a satisfactory alternative for the determination of organic phosphorus in human milk.

Acids↗

Specificity of human milk bile salt-stimulated lipase.

A crude preparation of the bile salt-stimulated lipase in human milk did not differentiate between the primary and secondary esters of several synthetic triacylglycerols. The dioleoyl ester of 2,3-butanediol was also digested, unequivocal confirmation of the absence of positional specificity. Preferential release of 18:2 relative to 16:0 and 18:1 as compared to 18:1t (trans) was observed. The lipase did not differentiate between 16:0 and 18:1 or 16:0 and 18:0.

Bile Acids and Salts↗

Prognostic groups for management of localized Hodgkin's disease.

Two hundred fifty-two patients receiving radical irradiation for clinical stages I and II Hodgkin's disease between 1968 to 1977 had an actuarial ten-year survival rate of 78% and a relapse-free rate of 61%. Sixty-seven patients receiving chemotherapy followed by radiation had a 78% survival rate and a 63% relapse-free rate. Independent prognostic factors for survival and relapse were age, stage, and histology. Disease bulk was predictive only of relapse. Neither site of presentation above or below the diaphragm nor presence of mediastinal involvement was predictive for survival or relapse; however, patients with large mediastinal masses (greater than or equal to 10 cm absolute diameter) had a significantly higher intrathoracic failure rate with conventional mantle irradiation. Analysis of failure, according to age, clinical stage, and histologic type, showed three groups of patients defined according to the risk of relapse with radiation therapy: those with isolated upper cervical stage IA disease (group 1, relapse rate 8%), younger patients with localized stages I and II disease of favorable histologic type (group 2, relapse rate 35%), and older patients with extensive or symptomatic stages I and II disease of less favorable histologic type (group 3, relapse rate 70%). Subsequent analysis of radiation treatment volume indicates that the use of upper abdominal irradiation for patients in group No. 2 could yield results equivalent to those achieved with radiation therapy for surgically staged patients.

Adolescent↗

Nitrogen distribution in human milk from 2 to 16 weeks postpartum.

The objective of this study was to determine how the major nitrogen components in human milk vary as total nitrogen in the milk changes. Milk samples were collected from 10 mothers at 2, 6, 12, and 16 wk postpartum. The major nitrogen components compared were total, nonprotein, urea, protein, casein, and whey nitrogens. Total nitrogen decreased from 2.18 mg/ml at 2 wk to 1.76 mg/ml at 16 wk. The percentage of nonprotein nitrogen was 19% and remained constant with time postpartum. Urea nitrogen averaged .14 mg/ml and also remained constant. Protein nitrogen decreased from 1.77 mg/ml at 2 wk to 1.42 mg/ml at 16 wk. As the total nitrogen in milk changed, the percentages of nonprotein nitrogen, whey nitrogen, and casein nitrogen remained relatively constant.

Female↗

Methods of lipid analysis.

A protocol for sample preparation before the determination in or isolation of lipids from human milk is presented. Methods for the direct determination of lipids including the creamatocrit, spectrophotometric (turbidimetric), and enzymatic methods are discussed. Procedures for the isolation of lipids including the Roese-Gottlieb, modified Folch, and dry column extractions are compared. Finally, techniques for the separation and identification of lipid classes are described.

Female↗