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Subdermal estradiol pellets following hysterectomy and oophorectomy. Effect upon serum estrone, estradiol, luteinizing hormone, follicle-stimulating hormone, corticosteroid binding globulin-binding capacity, testosterone-estradiol binding globulin-binding capacity, lipids, and hot flushes.

Subderman estradiol (E2) pellets (25 mg) were inserted immediately after hysterectomy and oophorectomy in 22 menstruating women, ages 29 to 50 years. Serum samples were obtained daily for 7 days, weekly for 4 weeks, and at monthly intervals for 6 months. Although there was significant variation between patients, E2 levels remained within the follicular phase range, averaging 50 to 70 pg/ml for 3 months, and then slowly declining to a mean of 37 pg/ml at 6 months, when new pellets were inserted. Over the entire study period, the E2:estrone (E1) ratio was greater than unity. Subdermal E2 pellets limited the rise in luteinzing hormone (LH) and follicle-stimulating hormone (FSH) after gonadectomy and the levels of LH and FSH 6 months after the insertion of E2 pellets were significantly lower (p < 0.01) than in 20 postmenopausal women who had undergone oophorectomy and whose serum E2 levels were less than 20 pg/ml. Serum corticosteroid binding globulin-binding capacity (CBG-BC) and serum testosterone-estradiol binding globulin-binding capacity (TeBG-BC) remained unchanged with E2 pellets. Although high-density lipoprotein-cholesterol increased significantly (p < 0.05), low-density lipoprotein-cholesterol, total cholesterol, and triglycerides were unaffected, except for a rise in triglycerides in three older women with diabetes mellitus and hypertension. There were no complaints of severe hot flushes. Women who had vasomotor symptaoms had mild or moderate flushes that occurred at 5 or 6 months after replacements of the pellets. Thus, E2 pellets are an effective form of parenteral estrogen replacement therapy and offer both practical and theorteical advantages over other forms of estrogen.

Adult↗

Alcohol and the heart. Intense hemodynamic changes associated with alcohol flush in orientals.

To evaluate the hemodynamic changes related to alcohol flush, the effects of ethanol intake (0.5 g/kg) were studied by echocardiography and systolic time intervals in 10 Finnish and 9 Japanese healthy volunteers. In 5 Japanese subjects, post-drink facial flush was associated with elevated blood acetaldehyde (peak levels 20-83 mumol/l) and marked cardiocirculatory stimulation. Heart rate was increased directly post ingestion by 65% (p less than 0.01), stroke index by 23% (p less than 0.05), and cardiac index by 106% (p less than 0.05). Diastolic blood pressure was simultaneously decreased by 23% (p less than 0.05), peripheral vascular resistance by 54% (p less than 0.01), and circumferential wall stress by 22% (p less than 0.05); ejection fraction was raised by 26% (p less than 0.01). The other Japanese and the Finnish subjects had no detectable acetaldehyde in blood after ethanol ingestion. The average hemodynamic alterations in them were similar in direction to the changes presented above, but quantitatively 6-10 times smaller (p less than 0.005 for each of these variables). Thus, in Orientals with genetically defective acetaldehyde oxidation, ingestion of even small amounts of alcohol evokes intense enhancement of left ventricular function, probably because of acetaldehyde-induced catecholamine release and peripheral vasodilation.

Acetaldehyde↗

Blockade of the 32P phosphate flush of pancreatic beta cells from adult rats who received a low-protein diet during early lactation.

In order to study the effect of nutrition on the onset of disturbances in Wistar rat pancreatic beta cells, we compared the effects of a low protein diet (8% protein) and a normal protein diet (25% protein) supplied to the dams (6 in each group) during the first 12 days of lactation. The parameter evaluated was the beta cells phosphate flush in response to stimulatory concentration of glucose (16.7 mM) of isolated islets of Langerhans from 60-day old pups. Using a collagenase digestion technique, islets were isolated from the pups and the 32P fractional outflow rate (FOR) of the beta cells was used as a metabolic index in both experimental groups (N = 36). We observed that although the weights of the pups of the two groups were not significantly different at 60 days of age (control = 186 +/- 18 g; undernourished during lactation = 179 +/- 19 g), the typical phosphate flush response (FOR = 2.4 +/- 0.4%/min) to a stimulatory glucose concentration (16.7 mM) was abolished in the rats from undernourished mothers. Our data are consistent with the hypothesis that undernutrition may be an important cause of diabetes mellitus type II.

Animals↗

[Microbiological public health aspects in the use of rain water as water reservoirs for toilet flushing, garden irrigation and laundry].

From a total of 102 rain water cisterns in use for toilet flushing, garden irrigation and laundering washing about 1,600 water samples were collected and subjected to microbiological analysis. The assays included aerobic heterotrophic microorganisms growing at 20 and 37 degrees C, respectively, as well as the identification of Escherichia coli, coliform organisms, faecal streptococci, Pseudomonas aeruginosa, staphylococci, yersiniae, salmonellae, shigellae, legionellae and yeasts. The median of the total number of cells per ml was 1,200 at 20 degrees C and 230 at 37 degrees C, respectively. Approximately 26 E. coli cells and 198 coliform organisms (median values) were found per 100 ml. In the case of cisterns manufactured of plastic the total number of cells was generally found to be lower than in samples collected from concrete or brick-made storage tanks. With the exception of the ubiquitously distributed organism Pseudomonas aeruginosa (found in 11.8% of the samples) and salmonella in only one sample, no other pathogens were detected. More than 95% of all analysed samples met the quality standards for bathing waters as set by the European Community. Provided certain precautions are taken, such as strict separation of mains for drinking water and rain water, as well as correct labelling of pipelines and collection sites, the use of rain water for toilet flushing, garden irrigation and laundry washing presents no unacceptable risk to public health.

Agriculture↗

Commercially available media for flushing extracorporeal bioartificial liver systems prior to connection to the patient's circulation: an in vitro comparative study in two and three dimensional porcine hepatocyte cultures.

Extracorporeal bioartificial liver (BAL) systems based on hepatocytes need to be flushed before clinical application, as hepatocyte culture media are not approved for medical use. Commercially available 0.9% NaCl solution and hemofiltration solution (both supplemented with 10% human albumin) were investigated in vitro to test their potential to wash BAL systems with minimal stress for the cultured hepatocytes. After a 2 hour incubation, the lidocaine metabolising capacity and release of liver enzymes were assessed. As hepatocytes have been cultured in bioreactors in either two or three dimensional cell configurations, we tested the media in respectively hepatocyte monolayers cultures and in our newly developed bioreactor in which hepatocytes reorganise as small hepatocyte aggregates. The three dimensional hepatocyte cultures tolerated both media well, and no significant differences were seen compared with hepatocytes cultured in Williams' E (reference hepatocyte culture medium). The two dimensional hepatocyte cultures tolerated the supplemented hemofiltration solution and the reference medium equally well, but the condition of the porcine hepatocytes monolayer cultures was significantly impaired when incubated with the supplemented physiological saline solution. In conclusion, as a supplemented physiological saline solution may have detrimental effects on the condition of the hepatocytes, the more complex hemofiltration solution (bicarbonate buffered, glucose, essential minerals) was considered the better alternative for flushing bioartificial liver systems.

Animals↗

Evidence for coronary spasm during flushing in the carcinoid syndrome.

In this report we present the history of a patient with symptomatic carcinoid syndrome. During flushing he suffered from variant angina. The observation of coronary spasm due to excess 5-hydroxytryptamine (5-HT) is discussed with regard to the discharge of 5-HT from clotting platelets in the coronary arteries.

Aged↗

Chlorpropamide-alcohol flush: significance of body weight, sex and serum chlorpropamide level.

Chlorpropamide-alcohol flush (CPAF) tests were carried out in 15 male and 15 female Type 2 diabetics. Twelve subjects were CPAF-positive and 18 were -negative. The two groups did not differ in age or duration of diabetes, but the CPAF-positive subjects weighed less (mean difference 13 kg) and had higher plasma chlorpropamide levels. There was a negative correlation between plasma chlorpropamide and body weight, and a positive correlation between plasma chlorpropamide and the increase in facial skin temperature. Females had higher plasma chlorpropamide, a greater skin temperature increase and lower body weight than males; there were 11 females and only 1 male amongst the 12 CPAF-positive subjects. The findings confirm that plasma chlorpropamide is a major determinant of the CPAF reaction and also show that body weight strongly influences the chlorpropamide level and, consequently, the outcome of the CPAF test. The sex difference in body weight probably accounts for most, if not all, of the sex difference in the incidence of the CPAF.

Body Weight↗

Association between chlorpropamide-alcohol flushing and fast acetylator phenotype in type I and type II diabetes.

Different prevalences of chlorpropamide alcohol flushing (CPAF) have been reported by different authors in either type I or type II diabetics or in normal subjects and this could be due to different methodological approaches or to different criteria of evaluation of CPAF. Previous studies in small series of patients have also suggested the existence of an association between type I diabetes and the fast acetylator phenotype (AP). The first aim of this study was to find reliable criteria for the assessment of CPAF. The second was to evaluate the prevalence of CPAF and of AP in a large series of type I and type II diabetics; and the third was to evaluate possible associations of CPAF and AP. AP and CPAF were evaluated separately in 256 diabetics (110 with type I and 146 with type II diabetes) and in 183 diabetics (74 with type I and 109 with type II diabetes), respectively. In 156 of these subjects, the two markers were evaluated together. The occurrence of CPAF was studied by subjective and objective assessment and by thermographic recording; CPAF was quantified by the differential value of skin temperature increase [delta T(C-P)] and by the value of differential speed of ascent, expressed in angle-degrees [delta a(C-P)], after treatment with placebo and with chlorpropamide. The fast AP was more frequent in type I than in type II diabetics, was not related to family history of diabetes, sex of the patients, age at onset and duration of diabetes or metabolic control. The most reliable assessment of CPAF was represented by thermographic recording of speed of ascent of skin temperature. CPAF was more frequent in females than in males, more frequent in diabetics than in healthy controls, similarly frequent in type I and in type II diabetes and showed no relationship with family history of diabetes, age at onset, duration of diabetes or metabolic control. An association between fast AP and CPAF was found in type II, but not in type I diabetics: fast acetylators were more frequently CPAF-positive, while slow acetylators were more frequently CPAF-negative. In addition, a linear relationship was found between rate of acetylation and speed of ascent of facial skin temperature after chlorpropamide and alcohol in type II diabetics, not in type I diabetics. The meaning of this association is not clear and deserves further investigations.

Acetylation↗

Transcutaneous iontophoresis of methadone provokes local flushing and thermal hyperalgesia.

OBJECTIVE: To investigate whether the introduction of methadone into the skin of the human forearm produces wheals, cutaneous vasodilatation or thermal hyperalgesia and, if so, to determine whether these responses are mediated by opioid receptors. SUBJECTS: Healthy adults. METHODS AND RESULTS: In Experiment 1 (N = 11), the increase in local blood flow (monitored with a laser Doppler flowmeter) was greater after the iontophoresis of methadone than saline (mean increase +/- S.D. 12.6 +/- 8.8 versus 2.2 +/- 1.9 times greater than baseline, p < 0.01). Flushing did not spread into surrounding skin and wheals did not form. In Experiment 2, pre-treatment with naloxone (N = 12) prevented increases in blood flow to methadone whereas saline pre-treatment (N = 14) did not. The heat pain threshold was lower at the site of methadone administration than at an untreated site (42.8 +/- 2.3 degrees C versus 44.6 +/- 1.7 degrees C, p < 0.001), and this effect was inhibited by naloxone pre-treatment. However, naloxone pre-treatment also antagonized an inhibitory effect of methadone on the pain generated by a 7-second pulse of 45 degrees C heat. In Experiment 3 (N = 11), the iontophoresis of methadone was repeated after an interval of 1.5 h. Vasodilatation to methadone persisted after the second iontophoresis, and sensitivity to heat was greater at a site of methadone administration than at a site of saline administration or an untreated control site. CONCLUSIONS: Stimulation of mu-opioid receptors dilated cutaneous blood vessels, and evoked local thermal analgesia and hyperalgesia at different stimulus intensities. However, stimulation of mu-opioid receptors did not produce wheals or flares.

Administration, Cutaneous↗

A preliminary evaluation of the effect of lofexidine on vasomotor flushes in post-menopausal women.

This is a preliminary study of a new orally administered alpha-adrenergic agonist, lofexidine, to establish its effectiveness in the control of vasomotor flushes (VMF) in five post-menopausal women. The initial dose of lofexidine, 0.1 mg b.i.d., was increased by 0.1 mg b.i.d. every two weeks until VMF disappeared, until side-effects became intolerable, or until a maximum dose of 0.6 mg b.i.d. was reached. When the maximum dose for these criteria was reached, there was a patient-blinded crossover to placebo. Each patient recorded her VMF each day and was monitored by finger thermistor for three hours every two weeks to record VMF. At the maximum tolerated dose, the patients had an average 74% (P less than 0.001) decrease in subjectively noted VMF, and a 61% (P less than 0.05) decrease in VMF objectively measured by finger thermistor. The side-effects (dry mouth, fatigue, headache) became intolerable for one patient at 0.3 mg b.i.d. and for one patient at 0.5 mg b.i.d. Two patients tolerated 0.6 mg b.i.d. Four patients had a return to near baseline numbers of VMF with placebo. Preliminary evidence indicates that lofexidine is probably effective in the treatment of VMF; however, at doses which completely eliminate VMF, the side-effects may become intolerable.

Clonidine↗

[Unilateral gustatory flushing syndrome in a child].

BACKGROUND: Auriculo-temporal syndrome is rarely seen in children: it is sometimes considered as secondary to an obstetrical injury. CASE REPORT: A 2.5 year-old boy was examined because he suffered from post-prandial flushing of the right cheek for 2 years. He was born normally and neurologic examination was normal. The rash was not associated with sweating or tearing. CONCLUSION: There is no evidence to support food allergy in this case: rather, this syndrome probably occurs in response to salivation.

Child, Preschool↗

Hot flushes during breast feeding?

The initiation of breast-feeding was accompanied by an increase in skin conductance followed by increased skin temperature. The pattern was similar to that observed during a menopausal hot flush and differed from sympathetic arousal and simple heating.

Body Temperature↗

[Facial vasomotor flushing due to alcohol-chlorpropamide. Prevalence in diabetic and non-diabetic patients].

Using a standard test (sherry 40 ml 12 hours and 36 hours after 250 mg chlorpropamide), chlorpropamide-alcohol flush (CPAF) prevalence was 34 p. 100 (19/56) in non insulin-dependent diabetics (NIDD), 10 p. 100 (3/30) in insulin-dependent diabetics and 7 p. 100 (2/27) in controls. Family history of diabetes was not associated with CPAF trait. Conflicting results in the literature might be explained by bias in patients selection or methodology.

Adult↗

On the relationship between methylnicotinate-induced skin flush and fatty acids levels in acute psychosis.

Vasodilation induced by methylnicotinate, a fatty acid- and cyclooxygenase-dependent process, is reduced or absent in patients with schizophrenia. This phenomenon has been suggested to be useful as a diagnostic test for the illness. To determine whether reduced flushing is specific to schizophrenia and is caused by a deficiency in membrane fatty acids, the extent of topically applied methylnicotinate-induced vasodilation was measured in 23 subjects with schizophrenia, 20 subjects with bipolar disorder and 34 healthy volunteers along with red cell fatty acid concentrations and measures of clinical severity. Although there was a significant decrease in an estimate of vasodilation (erythema) compared with healthy volunteers in both schizophrenia and bipolar groups, the schizophrenia group responded significantly less than subjects with bipolar disorder. The reduction in the bipolar group was partly due to a delayed vasodilatory reaction, an effect not observed in subjects with schizophrenia. In subjects with schizophrenia, there were no significant correlations between methylnicotinate response and fatty acid concentrations. The authors conclude that the methylnicotinate procedure can differentiate schizophrenia from other serious mental illness. The methylnicotinate insensitivity in schizophrenia, however, is likely to be due to a deficiency in the fatty acid precursors required for the vasodilatory reaction.

Administration, Topical↗

Niacin skin flush in schizophrenia: a preliminary report.

The aim of this pilot study was to evaluate a potential skin test for schizophrenia based on the effect of aqueous methyl nicotinate (AMN) on the production of prostaglandin D2 (PGD2) from skin macrophages and the resultant cutaneous capillary vasodilatation. Four concentrations of AMN were applied topically to the forearm skin in patients and controls, and any resulting vasodilatation was rated as redness after 5 min. The test was carried out on 38 patients with schizophrenia diagnosed according to DSM-III-R criteria, and 22 normal control subjects. At all concentrations of AMN, the schizophrenics were highly significantly different from the controls. One concentration gave the greatest degree of differentiation: at this concentration at 5 min, 83% of schizophrenics but only 23% of controls had a zero or minimal response to AMN. The skin flushing seen after oral administration of nicotinic acid is due to the same reaction, and this has been normal in those with affective illness and neurosis; cyclo-oxygenase inhibitors, e.g., aspirin, give a false-positive result (failure of vasodilatation). This result is consistent with the concept of reduced membrane arachidonic acid levels in schizophrenia. This test may contribute to the reliable diagnosis of schizophrenia.

Adult↗

Headache, circumoral paresthesia, and facial flushing associated with high-dose carmustine infusion.

We describe seven patients who developed symptoms including severe headache, circumoral paresthesia, and facial flushing during high-dose carmustine (BCNU) infusion as part of the preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation for metastatic breast cancer. Five patients responded to pain medications, including partial and complete opiate receptor agonists. Premedication of subsequent doses of BCNU with corticosteroids, pain medications, or benzodiazepines lessened, but did not prevent the same symptoms from recurring. The incidence and mechanism of this toxicity are unknown, but this adverse syndrome should be considered when administering high-dose BCNU infusions.

Antineoplastic Agents, Alkylating↗

Prostacyclin and thromboxane in non-insulin dependent diabetes: the chlorpropamide alcohol flush reaction revisited.

Levels of immunoreactive 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) and thromboxane B2 (TXB2) were measured in peripheral venous plasma in a group of volunteers and non-insulin dependent diabetic patients (NIDDS). Levels of these eicosanoids were close to the limit of sensitivity of the radioimmunoassays and consequently data are reported as maximal values. Basal plasma levels of 6-oxo-PGF1 alpha did not exceed 5 pg/ml in either group and maximal levels of immunoreactive TXB2 were 125 +/- 14 and 128 +/- 8 pg/ml for volunteers and NIDDS respectively. Attempts to elicit peripheral vascular prostacyclin biosynthesis in volunteers by using forearm ischaemia produced no increase in plasma 6-oxo-PGF1 alpha levels. Measurement of the combined plasma levels of 6-oxo-PGF1 alpha, 13,14-dihydro-6-oxo-PGF1 alpha, 13,14-dihydro-6,15-dioxo-PGF1 alpha and 6-oxo-PGE1 indicated that these were also low (less than 5 pg/ml) and that failure to demonstrate increased 6-oxo-PGF1 alpha levels was unlikely to have arisen from metabolism of prostacyclin to one or more of these metabolites. Measurement of 6-oxo-PGF1 alpha and TXB2 in peripheral venous plasma before and during chloropropamide alcohol flushing (CPAF) did not provide evidence for a role for these eicosanoids in the etiology of this phenomenon. These findings point to the need for a reappraisal of studies that have described altered plasma levels of 6-oxo-PGF1 alpha and TXB2 in CPAF and other pathophysiological conditions in man.

6-Ketoprostaglandin F1 alpha↗

Treatment of an acute flush reaction caused by subcutaneous r-hirudin with pegylated hirudin.

We report a patient who was treated with recombinant (r)-hirudin for heparin-induced thrombocytopenia and developed a flush reaction twice upon re-exposure to 25 mg of subcutaneous r-hirudin. Antihirudin IgG antibodies developed. The patient received 50 mg of PEG-hirudin subcutaneously over 2 days. No side-effects occurred. The level of IgG antihirudin antibodies increased. Ecarin clotting time and thrombin inhibition S2238 assay were not influenced by the patient's IgG antihirudin antibody. PEG-hirudin may be used in patients with intolerance to r-hirudin because of a dissociation of the allergenic and immunogenic properties of the pegylated drug.

Acute Disease↗