Regional cerebral tissue oxygen saturation changes following blood transfusion in neuro-intensive care unit patients - a pilot observational study.

BACKGROUND: Although central venous oxygen saturation (ScvO2 ) is used to decide on red blood cell (RBC) transfusion, whether its improvement is associated with parallel improvement in cerebral oxygenation is not adequately studied. This study looked at changes in regional cerebral tissue oxygen saturation (rSO2 ) following RBC transfusion in neuro-intensive care unit (ICU) patients. METHODS: In this prospective observational pilot study, rSO2 was measured in adult neuro-ICU patients before RBC transfusion, at the end and at 6, 12, 18 and 24 h after RBC transfusion. rSO2 measurements were taken using cerebral oximetry on both sides of the hemicraniums. Haemoglobin, central venous pressure, ScvO2 and temperature were recorded during the study period. Arterial oxygen content, central venous oxygen content and cerebral fractional oxygen extraction were calculated. Mann Whitney U test was used to study the changes in variables at baseline and at 24 h following RBC transfusion. Friedman's test was used to study changes in parameters from baseline to 24 h post-transfusion. A P value of <0·05 was considered to be significant. RESULTS: The data from 13 subjects were analysed. rSO2 increased significantly following RBC transfusion on both sides of the brain (P = 0·002, P = 0·007), with a corresponding decrease in cerebral fractional oxygen extraction (P = 0·001, P = 0·007). CONCLUSIONS: RBC transfusion increased rSO2 significantly on both sides of the brain. As patients' outcomes were not studied, whether this increase in regional cerebral oxygen saturation is beneficial or if it is because of excess DO2 is still unclear. Further studies are required to clarify this issue.

The effect of an ipriflavone-containing supplement on urinary N-linked telopeptide levels in postmenopausal women.

Osteoporosis is a significant health concern to our aging population. We report here the results of a pilot placebo-controlled trial of a dietary supplement containing ipriflavone, calcium, and vitamin D on a urinary marker of bone breakdown in postmenopausal women. Seven postmenopausal women not currently receiving hormone replacement therapy received either an ipriflavone-containing supplement or placebo for 3 months. Urinary N-linked telopeptides, a marker of bone breakdown, declined by 29% in those receiving the supplement, whereas an increase in this marker was observed in the group receiving the placebo. No changes were observed in salivary hormone measurements. Although our sample size was small, to the best of our knowledge, this is the first report that demonstrates changes in N-linked telopeptide levels as a result of consuming an ipriflavone-containing product. Our findings confirm those of other researchers that demonstrate the usefulness of ipriflavone at slowing the progression of bone loss and suggest that measuring N-linked telopeptides may be a useful tool to assess therapeutic efficacy.

Glucosylated glycerophosphoethanolamines are the major LDL glycation products and increase LDL susceptibility to oxidation: evidence of their presence in atherosclerotic lesions.

Glycation of both protein and lipid components is believed to be involved in LDL oxidation. However, the relative importance of lipid and protein glycation in the oxidation process has not been established, and products of lipid glycation have not been isolated. Using glucosylated phosphatidylethanolamine (Glc PtdEtn) prepared synthetically, we have identified glycated diacyl and alkenylacyl species among the ethanolamine phospholipids in LDL. Accumulation of these glycation products in LDL incubated with glucose showed a time- and glucose concentration-dependent increase. LDL specifically enriched with Glc PtdEtn (25 nmol/mg protein) showed increased susceptibility to lipid oxidation when dialyzed against a 5-micromol/L Cu(2+) solution. The presence of this glucosylated lipid resulted in a 5-fold increase in production of phospholipid-bound hydroperoxides and 4-fold increase in phospholipid-bound aldehydes. Inclusion of glucosylated phosphatidylethanolamine in the surface lipid monolayer of the LDL resulted in rapid loss of polyunsaturated cholesteryl esters from the interior of the particle during oxidation. Glycated ethanolamine phospholipids were also isolated and identified from atherosclerotic plaques collected from both diabetic and nondiabetic subjects. The present findings provide direct evidence for the previously proposed causative effect of lipid glycation on LDL oxidation.

Glycated phosphatidylethanolamine promotes macrophage uptake of low density lipoprotein and accumulation of cholesteryl esters and triacylglycerols.

Non-enzymatic glycation of low density lipoprotein (LDL) has been suggested to be responsible for the increase in susceptibility to atherogenesis of diabetic individuals. Although the association of lipid glycation with this process has been investigated, the effect of specific lipid glycation products on LDL metabolism has not been addressed. This study reports that glucosylated phosphatidylethanolamine (Glc-PtdEtn), the major LDL lipid glycation product, promotes LDL uptake and cholesteryl ester (CE) and triacylglycerol (TG) accumulation by THP-1 macrophages. Incubation of THP-1 macrophages at a concentration of 100 micrograms/ml protein LDL specifically enriched (10 nmol/mg LDL protein) with synthetically prepared Glc-PtdEtn resulted in a significant increase in CE and TG accumulation when compared with LDL enriched in non-glucosylated PtdEtn. After a 24-h incubation with LDL containing Glc-PtdEtn, the macrophages contained 2-fold higher CE (10.11 +/- 1.54 micrograms/mg cell protein) and TG (285.32 +/- 4.38 micrograms/mg cell protein) compared with LDL specifically enriched in non-glucosylated PtdEtn (CE, 3.97 +/- 0.95, p < 0.01 and TG, 185.57 +/- 3.58 micrograms/mg cell protein, p < 0.01). The corresponding values obtained with LDL containing glycated protein and lipid were similar to those of LDL containing Glc-PtdEtn (CE, 11.9 +/- 1.35 and TG, 280.78 +/- 3.98 micrograms/mg cell protein). The accumulation of both neutral lipids was further significantly increased by incubating the macrophages with Glc-PtdEtn LDL exposed to copper oxidation. By utilizing the fluorescent probe, 1,1'-dioctadecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate (DiI), a 1.6-fold increase was seen in Glc-PtdEtn + LDL uptake when compared with control LDL. Competition studies revealed that acetylated LDL is not a good competitor for DiI Glc-PtdEtn LDL (5-6% inhibition), whereas glycated LDL gave an 80% inhibition, and LDL + Glc-PtdEtn gave 93% inhibition of uptake by macrophages. These results indicate that glucosylation of PtdEtn in LDL accounts for the entire effect of LDL glycation on macrophage uptake and CE and TG accumulation and, therefore, the increased atherogenic potential of LDL in hyperglycemia.

The incidence of post-vasectomy chronic testicular pain and the role of nerve stripping (denervation) of the spermatic cord in its management.

OBJECTIVE: To assess the incidence of chronic postvasectomy testicular pain (CPTP) and evaluate the use of denervation of the spermatic cord in its management. PATIENTS AND METHODS: A retrospective postal survey of 560 patients (mean age 36 years, range 25-55; mean time since vasectomy 19 months, range 8-39) who underwent vasectomy between July 1992 and December 1994 was carried out to determine the incidence of CPTP. A prospective study was conducted in a further group of 17 patients (mean age 43 years, range 34-60), who had had CPTP for at least one year, to evaluate the effectiveness of nerve stripping of the spermatic cord in relieving pain. RESULTS: Of 396 replies, 108 (27.2%) patients complained of some testicular pain following their vasectomy operation. In 88 (82%) of these 108 patients the pain was brief and was not defined as CPTP, while 20 (19%) patients had pain for > 3 months; 33 (31%) patients required analgesics to control the pain. Of the 17 patients who underwent spermatic cord denervation, 13 reported complete relief of pain at their first follow-up visit and were discharged. Four patients had a significant improvement in the symptom score and were satisfied with the results. CONCLUSIONS: There is a small but significant incidence of CPTP and patients should be warned of this possibility when counselled before operation. Denervation of the spermatic cord seems to be a viable surgical option for patients with CPTP who fail to respond to conservative measures.

Effects of freezing and azide treatment of in vitro human skin on the flux and metabolism of 8-methoxypsoralen.

Clinical and in vitro evidence suggests that the physicochemical properties of the skin influence the process by which drugs are transported through skin. The effects of skin storage, preparation and pretreatment on the permeation and metabolism of (8-methoxypsoralen (8-MOP), as a model penetrant, were studied using the flow-through in vitro cell diffusion system. The metabolites and unchanged drug were estimated by thin-layer chromatography. While the permeability of 8-MOP was similar in fresh (445 cm.h-1) and azide-treated (449 cm.h-1) skin (p < 0.01), decreased permeability was observed in frozen skin (406 cm.h-1, p < 0.01). A 2.8-fold increase in the cumulative flux of 8-MOP at 24 h through azide-pretreated (2.5 x 10(-3) mumol.h-1.cm-1) versus fresh skin (9.1 x 10(-4) mumol.h-1.cm-1) was observed (p < 0.01). There was a slight increase in the flux of 8-MOP at 24 h when skin was frozen, compared with untreated skin. Increase in the flux of 8-MOP in frozen skin might result from the alteration of the molecular arrangement of the skin components during freezing. In addition to the obvious differences between frozen and fresh skin, these observations discourage the use of frozen skin. There is a moderate relationship between the permeability and flux of 8-MOP through frozen skin. A similar but nonrelated correlation was observed between the permeability and flux of 8-MOP through azide-treated skin samples (r = 0.6). These findings suggest that azide and freezing treatments lower the skin barrier properties to the transport of 8-MOP. Apparently, factors that may affect the inherent permeability of human skin, particularly those related to the handling, storage and pretreatment of skin with solvents and chemicals, can also influence topical drug delivery. The metabolic capacity of frozen skin and fresh skin remained constant during the period of study. These data may be of value in the development of topical methoxypsoralen systems. Further in vitro and in vivo studies are required to ascertain the generalization of this process.

Comparative study of repair of incisional hernia.

Repair of incisional hernias was compared with four different techniques in 55 patients to determine the best method of repair with least chance of recurrence. The maximum incidence of incisional hernia was seen in 30-39 years age group and was most frequently seen after gynaecological surgery (37 cases). Forty eight (88%) patients were operated in emergency by trainee surgeons. Most hernias occurred within one year after surgery and the herniation of lower mid line incision was more frequent (70.9% cases). History of wound infection of previous surgery was recorded in 45.5% of cases which appeared to be the important risk factor in causation of incisional hernia. It was also observed that simple repair of incisional hernia was associated with a high recurrence than that where synthetic mesh was used in repair where no recurrence was recorded.

Assessment of various techniques for the quantitative extraction of lysophospholipids from myocardial tissues.

Lipid extraction methods were evaluated for their effectiveness in extracting lysophosphatidylcholines and lysophosphatidylethanolamines from tissues and for subsequent recoveries during purification of crude extracts. The acid-butanol technique, although effective in complete extraction, resulted in partial hydrolysis (2-10%) of phospholipids containing 1-alk-1'-enyl-2-acylglycerophospholipids (plasmalogens) to produce artifactual lysophospholipids. This problem was avoided using a neutral butanol extraction or Bligh and Dyer techniques, but these resulted in only partial recoveries (60-72 and 75-80%, respectively) of these lipids. Tissue extracted with neutral chloroform-methanol mixtures provided virtually complete extraction (97-100%), but subsequent losses (up to 15%) occurred during purification of crude extracts with Folch synthetic upper phases. These losses could be circumvented by purification of the crude extract on Sephadex G-25 column. As an alternative, the Folch extraction technique was modified to achieve complete recoveries of lysophospholipids. This involved extraction of the tissue with a chloroform-methanol-saline biphasic system. After removal of the lower lipid phase, the upper phase containing residual tissue was reextracted twice more with Folch lower phase and once with lower phase containing HCl. This last extract was neutralized with NH3 vapor before pooling with the preceding extracts. This method (i) circumvents plasmalogenic hydrolysis, (ii) avoids use of time-consuming column chromatography, (iii) eliminates the losses of lipids during purification, and (iv) allows highly reproducible quantitative analyses of all lipid fractions including lysophospholipids and nonesterified fatty acids from myocardial tissue.

Alterations in fatty acid metabolism in adriamycin cardiomyopathy.

Myocardial fatty acid metabolism may be impaired in adriamycin cardiomyopathy. In order to determine the extent of fatty acid metabolism alterations, we measured steady state [14C]palmitate oxidation and the incorporation of [14C]palmitate into the neutral lipid pool in a rat model of adriamycin cardiomyopathy. Isolated hearts from control rats and rats treated with adriamycin were perfused with 1.2 mmol/l of [14C]palmitate for 30 min to achieve steady state oxidation measured as [14C]O2 production; then perfused with 1.2 nmol/l of unlabelled palmitate. Hearts were killed early (0-5 min) or late (10-30 min) after the [14C]palmitate perfusion, to determine incorporation into the neutral lipid pool, and neutral lipid utilization. In the control group steady state oxidation was reached in 10 min ([14C]O2 production = 580 +/- 61 nmol/min/g dry wt) of perfusion. In the adriamycin treated group, mean CO2 production was significantly reduced at 10 min (329 +/- 44 nmol/min/g dry wt, P < 0.01 v control). At 30 min, [14C]O2 production in the treated group was not significantly different than controls (521 +/- 65 nmol/min/g dry wt v 617 +/- 36 nmol/min/g dry wt, P = N.S.). The incorporation of [14C]palmitate into the neutral lipid pool measured in the early subgroup was significantly reduced for adriamycin treated hearts v controls (7.2 +/- 0.6 v 12.0 +/- 1.4 mumol/g dry wt respectively, P < 0.01). In the control group 14C labelled neutral lipid reduced with time to 8.4 +/- 1.1 mumol/g dry wt (P < 0.05) in the late group. The adriamycin group demonstrated no significant change between early and late measurements. In conclusion, in adriamycin cardiomyopathy: (1) there is significant delay in achieving steady state palmitate oxidation, although the steady state rate is near normal; (2) palmitate incorporation into the neutral lipid pool is reduced; (3) neutral lipid pool utilization may also be reduced. These data suggest impaired uptake of palmitate into the cell in adriamycin cardiomyopathy, with a relatively maintained capacity for oxidative metabolism.

Phospholipase inhibition and the electrophysiology of acute ischemia: studies with amiodarone.

Previous studies have shown a close temporal relationship between lipid abnormalities and membrane dysfunction in ischemia and that phospholipase-inhibiting drugs limit such derangements. Amiodarone is a potent phospholipase inhibitor, but its potential or that of any other inhibitor to simultaneously attenuate lipid abnormalities and electrophysiological changes in the very early phase of ischemia has never been studied. We therefore investigated simultaneously such changes in early ischemia. In isolated porcine hearts perfused with or without pure amiodarone solutions, electrophysiologic changes before and during 20 min of LAD occlusion were recorded using unipolar electrodes and Franz contact electrode catheters, and full thickness myocardial biopsies obtained for lipid analyses. In untreated hearts (n = 5), occlusion of LAD resulted in the rapid onset of TQ depression/ST elevation within 1 min and plateauing at 10 min. There were mean increases of 33% and 50% in lysophosphatidylcholine and 33% and 70% in lysophosphatidylethanolamine levels at 5-7 min and 20 min of ischemia, respectively. Non-esterified fatty acid (NEFA) content did not change significantly during the first 5-7 min, but increased by 75% after 20 min of LAD occlusion. In treated hearts (n = 5) there was a 37% increase in sinus cycle length after amiodarone administration (503 +/- 85 vs 689 +/- 115 ms, P < 0.01) but no significant change in ventricular effective refractory period (202 +/- 22 vs 204 +/- 21 ms), action potential duration (215 +/- 11 vs 217 +/- 7 ms), or amplitude (31 +/- 6 vs 28 +/- 3 mV) was observed. Also, amiodarone treatment did not alter total phospholipid content, lysophospholipids and NEFA levels of non-ischemic hearts. However, there was significant attenuation (P < 0.01) of the onset of the TQ/ST shift and preservation of action potential amplitude (P < 0.02) during the first 5-7 min of LAD occlusion with concomitant suppression of the increase in both lysophospholipids (hydrolysis products of membrane phospholipids by endogenous phospholipases) and NEFA levels observed after 5-7 and 20 min of ischemia. The results suggest that amiodarone can delay the onset and limit the extent of electrophysiologic change in early myocardial ischemia in temporal association with suppression of myocardial phospholipase activities.

Effect of amiodarone therapy on the time course of myocardial phospholipid hydrolysis during in vitro total ischaemia in cat hearts.

The effects of chronic amiodarone therapy on myocardial phospholipid hydrolysis induced by total in vitro ischaemia were investigated in cat hearts. Chronic treatment of cats with amiodarone (30 mg/kg/day, orally) for 6 weeks resulted in a sufficient uptake of the drug reaching tissue levels of 83 +/- 13 & 122 +/- 22 microM (n = 12) for amiodarone and its principle metabolite, desethylamiodarone, respectively. This was accompanied by a significant increase (37%, P less than 0.001) in total phospholipid content of heart in treated as compared to untreated animals. Upon in vitro total ischaemia, these endogenous drug levels were sufficient to attenuate significantly hydrolysis of membrane phospholipid. The degree of attenuation was dependent upon the duration of ischaemic insult. In this regard, protection against phospholipid losses by amiodarone treatment was significantly more in the later irreversible phase of ischaemic injury whether studied in an in vitro total ischaemia model or in an isolated perfused heart preparation. Similar trend was observed in the relative accumulation of lysophospholipid and non-esterified fatty acid levels during ischaemia, i.e. both were significantly attenuated by amiodarone treatment. However, in contrast to the fatty acid data, the net changes in lysophospholipids per gram tissue wet weight were similar in treated and untreated animals, suggesting that the protective effects of amiodarone may have involved other enzymes including phospholipase C and D. Also, during the entire time course studied, all the phospholipid classes appeared to be affected to more or less a similar degree, indicating that the effects of the drug may have manifested in other subcellular compartments besides lysosomes. However, at all time periods studied, the net release of eicosatetraenoic and docosahexaenoic acid (fatty acids occupying primarily sn-2 position of phospholipids) was different, release of the former fatty acid being inhibited more than the latter, suggesting specific interaction of amiodarone with the molecular species of phospholipid. The data suggest that amiodarone attenuates ischaemia-induced membrane lipid abnormalities in part through modulation of phospholipid metabolism, and that this effect may be one of the key determinants which contribute to its antiarrhythmic properties during acute ischaemia.

Analysis by DNA polymerase alpha activity of human breast tumour proliferation and the effect of endocrine therapy.

Cytosols of human breast tumours have been assayed for DNA dependent DNA polymerase alpha activity. DNA polymerase alpha activity in benign tumours was found to be significantly lower than in untreated malignant tumours. Biopsy samples removed surgically before and after endocrine therapy showed reduced DNA polymerase alpha activity in 6 out of 9 patients treated with 4-hydroxyandrostenedione, and in 6 out of 7 patients treated with MPA. DNA polymerase alpha activity in malignant breast tumours was higher in oestrogen receptor negative than oestrogen receptor positive tumours.

Characterization and analysis of the subclasses and molecular species of choline phosphoglycerides from porcine heart by successive chemical hydrolyses and reverse phase high-performance liquid chromatography.

Choline phosphoglycerides (CPG) represent the major fraction of heart phospholipids. Since depletion of membrane phospholipids and accumulation of lyso-compounds, particularly lysophosphatidylcholines, have been implicated in arrhythmogenesis, it was of great interest to study the composition of this major phospholipid fraction of the heart at a molecular level in an established animal model. The data presented here describe the first report on the detailed chemical examination of CPG and resolution, characterization and quantitative analysis of the molecular species of this phospholipid fraction from porcine heart by high performance liquid chromatography (HPLC). This fraction constitutes 37.5 +/- 0.7% (n = 21) of the total phospholipids and upon successive mild acid and alkaline hydrolyses revealed the presence of essentially three subclasses: diacyl-, alkenylacyl-, and alkylacyl glycerophosphorylcholines, in a relative abundance of 57.7 +/- 2.2% (n = 8), 37.3 +/- 1.3% (n = 8) and 4.6 +/- 0.2% (n = 8), respectively. The fourth subclass, dialkyl CPG was found only in minute amounts (0.43 +/- 0.05%, n = 8) and the presence of dialkenyl and alkenylalkyl analogues could not be detected. Alternatively, by converting the CPG fraction to benzoate derivatives after phospholipase C digestion, it was possible to isolate and quantitate subclass composition by TLC/spectroscopy or both subclass compositions and molecular species analysis by HPLC directly by a UV detector online with the column. By these techniques, subclass composition was found to be very similar to that obtained by the chemical hydrolysis technique. By HPLC, up to 25 species can be identified and quantitated in each subclass, their identity being confirmed by gas-liquid chromatography, after their isolation from the column. The analyses showed that up to 74% of the diacyl moiety consisted of 16:0-18:2 (34%), 16:0-18:1 (27%), and 18:0-18:2 (13%) species, while the major species of the alkenylacyl moiety were 16:0-18:2 (44%) 16:0-18:1 (13%), 16:0-20:4 (12%) and 18:1-18:2 (9%) making up more than 75% of the total mass of this subclass. The major molecular species of the alkylacyl moiety was 16:0-18:2, constituting up to 47% of this fraction, while others constituted about 10% (16:0-18:1), 9% (18:1-18:2), 8% (16:0-20:4) and 6% (18:0-18:2), making up 80% of the total mass. The ether chain composition of akylacyl CPG whether determined after isolation of this fraction by the chemical hydrolysis technique or by HPLC was indistinguishable.(ABSTRACT TRUNCATED AT 400 WORDS)

Epidermal growth factor and oestradiol in human breast cyst fluid.

Gross cystic breast disease is a common condition in women. Women with apocrine breast cysts (breast cyst fluid Na+/K+ less than 3) may be at higher risk of breast cancer than women who have cysts lined by flattened epithelium (Na+/K+ greater than or equal to 3). Breast cyst fluid concentrations of epidermal growth factor were significantly higher in the low electrolyte ratio group than in the high electrolyte ratio group (356.2 ng/ml vs 104.1 ng/ml, P less than 0.0003). A negative correlation was obtained between intracystic epidermal growth factor concentrations and Na+/K+ (rs = -0.666, P less than 0.001). No significant difference was found between the total oestradiol concentrations in the two cyst groups. However, the unbound oestradiol concentrations on a limited number of samples were significantly higher in the low electrolyte ratio group than in the high electrolyte ratio group (P less than 0.05). The higher concentrations of EGF in cyst fluid with Na+K+ less than 3 may explain why women with apocrine breast cysts may be at increased risk of developing breast cancer.

Effect of treatment with 4-hydroxyandrostenedione on the peripheral conversion of androstenedione to estrone and in vitro tumor aromatase activity in postmenopausal women with breast cancer.

The effect of treatment with the aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA) on the peripheral conversion of androstenedione to estrone has been examined in eight postmenopausal women with advanced breast cancer. Before treatment conversion of androstenedione to estrone ([p]AEIBB) ranged from 0.81 to 3.7% and was almost completely inhibited after treatment with 4-OHA (two doses of 500 mg i.m. with an interval of 12 days between doses). Transfer constants were also measured by the urinary method ([p]AEIBU) for some subjects and decreased from 2.3 +/- 0.52% to 0.24 +/- 0.11% after treatment, a mean reduction of 90%. Mean plasma concentration of estradiol (37.4 +/- 16.6 pmol/liter) and estrone (99.0 +/- 32.2 pmol/liter) decreased significantly (P less than 0.01) to 15.7 +/- 4.6 pmol/liter and 52.4 +/- 8.9 pmol/liter, respectively, after treatment. Aromatase and DNA polymerase alpha (a marker of cell proliferation) activities were measured in seven samples of breast tumor tissue obtained before and after treatment. For three samples there was a marked (67 +/- 17%) decrease in tumor aromatase activity after treatment, for two, little change occurred, while tumor aromatase activity in the other two samples appeared to be resistant to the effect of 4-OHA. The correlation between tumor aromatase and DNA polymerase alpha activities (r = 0.45) failed to reach a significant level.

Relationship between epidermal growth factor and dehydroepiandrosterone and its sulphate in breast cyst fluid.

Gross cystic breast disease is a common condition. Women with apocrine breast cysts may be at higher risk of breast cancer than women with cysts which are lined by flattened epithelium. Apocrine cysts have been shown to be associated with higher intracystic levels of dehydroepiandrosterone sulphate and intracystic sodium to potassium ratios of less than 3. In this study we measured the concentrations of epidermal growth factor, dehydroepiandrosterone and its sulphate in breast cyst fluid. The concentrations of all three analytes were significantly higher in cysts with intracystic Na+/K+ ratios of less than 3 than in cysts with electrolyte ratios of greater than or equal to 3 (P less than 0.001). The higher levels of EGF in cysts with low intracystic electrolyte ratios may provide an explanation of why women with apocrine cysts may be at greater risk of breast cancer. Positive correlations were obtained between concentrations of EGF and DHAS and between EGF and DHA, compatible with the view that intracystic EGF levels may be androgen-modulated. A positive correlation was also obtained between DHA and DHAS concentrations which supports the view that DHA in cyst fluid may be derived from the metabolism of DHAS in the breast cyst wall.