Evaluation of the signs and symptoms of pseudotumor cerebri syndrome in pediatric population.

PURPOSE: Pseudotumor cerebri syndrome (PTC) is characterized by increased intracranial pressure without a space-occupying lesion and a normal cerebrospinal fluid (CSF) composition without evidence of CSF infection. In this study, we aimed to compare the symptoms, signs, and clinical characteristics of patients presenting with a preliminary diagnosis of pseudotumor cerebri syndrome (PTC) who were diagnosed and not diagnosed with PTC. METHOD: We conducted a retrospective study of patients who were referred to our clinic with signs and symptoms of PTC. We compared the patients' symptoms, signs, and clinical characteristics who were diagnosed with PTC with those who were not diagnosed with PTC using modified Dandy criteria. RESULTS: Ninety-four patients with the pre-diagnosis of PTC were included in the study. LP procedure was done in all patients. After LP, 75.3% of the patients were diagnosed with PTC, but 24.7% did not meet the criteria for PTC. A statistically significant relationship was found between the increase in headache complaints when leaning forward, headache that keeps the child from playing, and the CSF pressure level (p = 0.014, p = 0.019; p < 0.05). There was no statistically significant correlation between papilledema and CSF pressure level (p > 0.05). A statistically significant relationship was found between papilledema grade and CSF pressure level (p = 0.038; p < 0.05), and the rate of high CSF pressure in the groups with Grades 2-3 and Grade 4 papilledema was higher than that in the group with Grade 1 papilledema. Cranial nerve 6 palsy (CN6) (p = 0.048) and flattening of the posterior aspect of the globe (FPS) are found independent risk factors (p = 0.004 p < 0.05). CONCLUSIONS: PTC signs and symptoms show variability among pediatric population.

Milk fatty acid profile from grazing buffaloes fed a blend of soybean and linseed oils / Perfil de ácidos graxos do leite de búfalas a pasto recebendo uma mistura de óleo de soja e linhaça na dieta

The aim of the study was to examine the changes in milk fatty acid (FA) profile of grazing buffaloes fed either low (L, 276g/d) or high (H, 572g/d) doses of a blend (70:30, wt/wt) of soybean and linseed oils. Fourteen multiparous Mediterranean buffaloes grazing on a native pasture were fed 4 kg/day of a commercial concentrate containing no supplemental oil over a pre-experimental period of ten days. The baseline milk production and composition and milk FA profile were measured over the last three days. After this pre-experimental period the animals received the same concentrate added with either the L or H oil doses for 26 additional days. Milk yield (g/animal/day) did not differ at the start (1776 ± 522 and 1662 ± 291 for L and H, respectively, P<0.622) or at the end of the trial (4590 ± 991 and 4847 ± 447 in L and H, respectively, P<0.543). Baseline milk fat content (g/kg) averaged 77.1 (±20.5) in L and 74.3 (±9.9) in H (P<0.10) and was reduced (P<0.031) to 60.7 (±23.6) and 49.4 (±11.2) (P<0.0031) respectively after L and H with no differences between treatments (P<0.277). Baseline milk protein content (L=43.2 ± 3.4 and H= 44.3 ± 6.9g/kg) increased after oil supplementation (P<0.0001) in both L (73.2 ± 6.0g/kg) and H (68.4 ± 4.9g/kg) without differences between oil doses (P<0.123). Milk fat content of 14:0 decreased after oil supplementation only in the H treatment (5.29 to 4.03, P<0.007) whereas that of 16:0 was reduced (P<0.001) at both L (24.49 to 19.75g/100g FA) and H (25.92 to 19.17g/100g FA) doses. The reduction of total content of 12:0 to 16:0 was higher (P<0.052) in H (32.02 to 23.93g/100g FA) than L (30.17 to 25.45g/100g FA). Vaccenic acid content increased (P<0.001) from 5.70 to 13.24g/100g FA in L and from 5.25 to 16.77 in H, with higher results in the in H treatment (P<0.001). Baseline rumenic acid was sharply increased (P<0.001) in L (1.80 to 4.09g/100g FA, +127%) and H (1.60 to 4.61g/100g FA, +187%) with no differences between...

O objetivo do presente estudo foi avaliar as mudanças no perfil de ácidos graxos do leite de búfalas leiteiras recebendo baixas (B, 276g/d) ou altas (A, 572g/d) doses de uma mistura de óleos de soja e linhaça (70:30, peso/peso) na dieta. Quatorze búfalas multíparas da raça Mediterrânea, mantidas em pastagens nativas, receberam 4kg/dia de um concentrado comercial sem adição de óleo (pré-tratamento) ao longo de umperíodopré-experimental de 10 dias. A produção de leiteindividual e amostras de leite foram coletadas individualmente para determinação dos valores basais de composição e perfil de ácidos graxos do leite nos últimos trêsdias. Após este período, os animais receberam o mesmo concentrado adicionado deBou Apor 26 dias. A produção de leite (g/animal/dia) não diferiu no início (1776 ± 522 e 1662 ± 291para B e A, respectivamente (P<0,622) e no final do período experimental(4590 ±991e4847 ± 447 para LeH, respectivamente, P<0,543). O teor de gordura do leite (g/100g) apresentou valores médios de 77,1(±20,5)paraBe74,3 (±9,9)paraA(P<0,10) durante o período pré-tratamento,mas foi reduzido (P<0,03) após o fornecimento das dietas com óleo para 60,7 (± 23,6) e 49,4 (± 11,2), respectivamente para B e A, não havendo diferenças entre tratamentos (P<0,277). Os teores basais de proteína do leite (B=43,2 ± 3,4 e A=44,3 ± 6,9g/kg) aumentaram após a suplementação com óleo (P<0,0001) em ambos B (73,2 ± 6,0g/kg) e A (68,4 ± 4,9g/kg), não ocorrendo diferenças entre tratamentos (P<0,123). O teor médio basal de 14:0 na gordura do leite (4,76g/100g AG) foi reduzido após a suplementação da dieta com óleo somente no tratamento A (5,29 para 4,03, P<0,007). O teor de 16:0 na gordura do leite foi reduzido (P<0,001) nos tratamentos B (24,49 para 19,75g/100g AG) e A (25,92 para 19,17g/100g AG). A redução nos teores de 12:0+14:0+16:0 na gordura do leite foi maior (P<0,052) em A (32,02 para 23,93g/100g AG) do que em B (30,17 para 25,45g/100g AG). O teor de ácido vacênico (AV)...

Effects of acute hypercalcaemia on blood pressure in subjects with and without parathyroid hormone secretion.

AIM: Acute hypercalcaemia increases the blood pressure, but the mechanism is uncertain. It may partly be the result of the concomitant fall in parathyroid hormone (PTH) secretion as PTH has been reported to have a vasodilator effect. To elucidate this, we infused calcium intravenously in subjects with and without PTH secretion. METHODS: Seven thyroparathyroidectomized subjects with undetectable PTH levels and 10 controls were studied twice, once with a calcium clamp technique that increased plasma ionized calcium in two steps of 0.1 mmol L(-1), each step lasting 60 min, and once with a placebo infusion. RESULTS: On the placebo day, blood pressure and all other variables were unaffected in both groups. On the calcium day, systolic blood pressure increased gradually and significantly from end of baseline till end of the calcium infusion in the controls (123.5 +/- 19.8 and 134.2 +/- 17.6 mmHg, P < 0.004) but not in the thyroparathyroidectomized subjects (124.9 +/- 15.7 and 126.0 +/- 20.6 mmHg, P = ns). Serum PTH levels fell promptly in the controls, and in both groups there was a significant increase in serum phosphate. The diastolic blood pressure and pulse rate, and the plasma adrenaline and noradrenaline, plasma renin activity, and serum aldosterone levels were unaffected by the calcium infusion. CONCLUSION: During acute hypercalcaemia the blood pressure increase appears unrelated to catecholamine secretion and the renin-aldosterone system, whereas the fall in PTH secretion may play a contributory role.

Reconstitution of ATP-dependent cGMP transport into proteoliposomes by membrane proteins from human erythrocytes.

The cellular efflux of cGMP from human erythrocytes has previously been characterized in functional studies. The purpose of the present study was to find membrane proteins with the ability to restore ATP-dependent uptake of cGMP into proteoliposomes. Human erythrocyte membranes were solubilized with CHAPS (3-([3-cholamidopropyl]dimethylammonio)-1-propanesulfonate) and gel filtration gave three protein fractions with the ability to restore active transport. Only two of these fractions were retained on a lentil lectin column. By using these two purification steps, active transport was 11 times higher in the first fraction compared to the original material and SDS-PAGE showed the presence of proteins with sizes of 145 kDa and 165 kDa. The second fraction gave 20 times higher active transport after purification and comprised proteins with sizes of 145 kDa and 180 kDa. At present three members of the MRP (multi-resistance associated protein) family have been detected in human erythrocytes: MRPI, MRP4 and MRP5. The last two proteins have been shown to transport cyclic nucleotides. The present findings are compatible with MRP4 as the 145 kDa protein, MRP5 as the 165 kDa protein and MRP1 as the 180 kDa protein. However, the 145 kDa protein could also be SMRP (short multi-resistance protein), the gene splice variant of MRP5. Immunoprecipitation of MRP5 from CHAPS-solubilized extract reduced active transport and specific binding by about 45% and 40%, respectively. This shows that MRP5 is an important cGMP-transporting protein in human erythrocytes.

Inhibition by guanosine cyclic monophosphate (cGMP) analogues of uptake of [(3)H]3',5'-cGMP without stimulation of ATPase activity in human erythrocyte inside-out vesicles.

The cellular extrusion of guanosine 3',5'-cyclic monophosphate (3',5'-cGMP) is a unidirectional ATP-dependent process that is inhibited by probenecid, a non-selective transport inhibitor of organic anions. In the present study, various cGMP analogues were tested for their ability to inhibit 3',5'-cGMP efflux and stimulate the cGMP-selective ATPase in human erythrocytes. The difference in uptake of 1 microM [(3)H]3',5'-cGMP to inside-out vesicles in the presence and absence of 1 mM ATP at 37 degrees was defined as active transport. Two ATP-dependent components were detected for unlabelled 3',5'-cGMP (0.01--100 microM) with respective K(i) of 1.3 +/- 0.2 and 280 +/- 50 microM (mean +/- SEM, N = 3). The high-affinity transport was inhibited by the analogues with a typical pattern: Rp-monophosphorothioate guanosine 3',5'-cyclic monophosphate (Rp-cGMPS) > 3',5'-cGMP > 2'-O-monobutyryl guanosine 3',5'-cyclic monophosphate (O-mb-cGMP) approximately N(2)-monobutyryl guanosine 3',5'-cyclic monophosphate (N-mb-cGMP) > or = N(2),2'-O-dibutyryl guanosine 3',5'-cyclic monophosphate (Db-cGMP) approximately 8'-bromo guanosine 3',5'-cyclic monophosphate (Br-cGMP) approximately Guanosine 2',3'-cyclic monophosphate (2'3'-cGMP) > Sp-monophosphorothioate guanosine 3',5'-cyclic monophosphate (Sp-cGMPS). A concentration-dependent inhibition was found for the low-affinity transport, but no distinct order of potency was identified. Analysis according to Lineweaver--Burk of active [(3)H]3',5'-cGMP transport (0.2--2 microM) gave a K(m) value of 1.5 +/- 0.1 microM (mean +/- SEM, N = 3). The presence of 10 microM cGMP analogues did not change the ordinate intercept, but made the slopes steeper with a typical order: Rp-cGMPS > 3',5'-cGMP > N-mb-cGMP approximately O-mb-cGMP approximately db-cGMP approximately 8-Br-cGMP > 2',3'-cGMP > Sp-cGMPS. Only 3',5'-cGMP and 2',3'-cGMP were able to activate the cGMP-specific ATPase, 640 +/- 200% and 430 +/- 160% (mean +/- SEM, N = 5) above basal levels, respectively. The present data show that the binding is less selective than ATPase activation of the cellular cGMP transport system.

An iron-regulated ferric reductase associated with the absorption of dietary iron.

The ability of intestinal mucosa to absorb dietary ferric iron is attributed to the presence of a brush-border membrane reductase activity that displays adaptive responses to iron status. We have isolated a complementary DNA, Dcytb (for duodenal cytochrome b), which encoded a putative plasma membrane di-heme protein in mouse duodenal mucosa. Dcytb shared between 45 and 50% similarity to the cytochrome b561 family of plasma membrane reductases, was highly expressed in the brush-border membrane of duodenal enterocytes, and induced ferric reductase activity when expressed in Xenopus oocytes and cultured cells. Duodenal expression levels of Dcytb messenger RNA and protein were regulated by changes in physiological modulators of iron absorption. Thus, Dcytb provides an important element in the iron absorption pathway.

ATPase activity and transport by a cGMP transporter in human erythrocyte ghosts and proteoliposome-reconstituted membrane extracts.

We previously described the [(3)H]cGMP-binding characteristics of a CHAPS-solubilized protein that we proposed to be a cGMP transporter. We now report the ATPase activity of the membrane-bound, solubilized and reconstituted form of a cGMP transporter. The membrane-bound protein of unsealed ghosts had a linear ATPase activity over a 120 min incubation period with optimal activity of about 400 pmol/mg/min. The apparent K(m) and V(max) for ATP were about 0.5 mM and 300 pmol/mg/min, respectively. When solubilized with CHAPS the specific activity of the protein was reduced to about 70 pmol/mg/min. Reconstitution of the CHAPS preparation into phospholipid bilayer using rapid detergent removal by Extracti-gel column resulted in proteoliposomes which had ATPase activity similar to that found in the erythrocyte membranes. The proteoliposomes displayed a linear ATP-dependent uptake of [(3)H]cGMP with an apparent K(m) value of 1. 0 microM. This low K(m)-uptake of [(3)H]cGMP in proteoliposomes was not affected by 10 microM of AMP, cAMP and GMP, but was completely abolished in the presence of the non-hydrolyzable ATP analogue, ATP-gamma-S. Some ATPase activation was also observed in the presence of 2 microM cAMP, but it is unclear whether this activity was coupled to the cGMP transporter. Our results show that the membrane protein responsible for cGMP transport has an ATPase activity and transports the cyclic nucleotide in the presence of ATP.

Leukotriene C(4) (LTC(4)) does not share a cellular efflux mechanism with cGMP: characterisation of cGMP transport by uptake to inside-out vesicles from human erythrocytes.

The transport of cGMP out of cells is energy requiring and has characteristics compatible with an ATP-energised anion pump. In the present study a model with inside-out vesicles from human erythrocytes was employed for further characterisation of the cGMP transporter. The uptake of leukotriene C(4) (LTC(4)), a substrate for multidrug resistance protein (MRP), was concentration-dependently inhibited by the leukotriene antagonist MK571 (IC(50)=110+/-20 nM), but cGMP was unable to inhibit LTC(4) uptake. Oxidised glutathione (GSSG) and glutathione S-conjugates caused a concentration-dependent inhibition of [(3)H]cGMP uptake with IC(50) of 2200+/-700 microM for GSSG, 410+/-210 microM for S-(p-nitrobenzyl)glutathione and 37+/-16 microM for S-decylglutathione, respectively. Antioxidants such as reduced glutathione and dithiothreitol did not influence transport for concentrations up to 100 microM, but both inhibited cGMP uptake with approx. 25% at 1 mM. The cGMP pump was sensitive to temperature without activity below 20 degrees C. The transport of cGMP was dependent on pH with maximal activity between pH 8.0 and 8.5. Calcium caused a concentration-dependent inhibition with IC(50) of 43+/-12 microM. Magnesium gave a marked activation in the range between 1 and 20 mM with maximum effect at 10 mM. The other divalent cations, Mn(2+) and Co(2+), were unable to substitute Mg(2+), but caused some activation at 1 mM. EDTA and EGTA stimulated cGMP transport concentration-dependently with 50% and 100% above control at 100 microM, respectively. The present study shows that the cGMP pump has properties compatible with an organic anion transport ATPase, without affinity for the MRP substrate LTC(4). However, the blockade of the cGMP transporter by glutathione S-conjugates suggests it is one of several GS-X pumps.

The effect of Mg2+, nucleotides and ATPase inhibitors on the uptake of [3H]-cGMP to inside-out vesicles from human erythrocytes.

An ATP-dependent transport system is responsible for the cellular extrusion of cGMP. The objective of the present study was to determine the effect of Mg2+, ATP and other nucleotides (2'-dATP, GTP and ADP), exogenous ATPase modulators (such as metavanadate, ouabain, EGTA, NEM, bafilomycin A1 and oligomycin A) on the cGMP transport. The uptake of [3H]-cGMP (1 microM) at 37 degrees C was studied in inside-out vesicles from human erythrocytes. Magnesium caused a maximal activation between 5 and 10 mM and the optimal ATP concentration was 1.25 mM with K50-values of 0.3-0.5 mM. Among other nucleotides tested, 2'-dATP (K50 of 0.7 mM) was nearly as effective as ATP, whereas cGMP accumulated slowly in the presence of GTP. ADP and metavanadate (P-type ATPase inhibitor) showed to be competitive inhibitors with Ki values of 0.15 mM and 10 microns, respectively. NEM (a sulphydryl agent) reduced the ATP-dependent uptake in a concentration-dependent manner with a Ki value of 10 microM. Ouabain (Na+/K(+)-ATPase inhibitor) had no effect. Bafilomycin A1 (V-type ATPase inhibitor) and oligomycin (F-type ATPase inhibitor) were the most potent inhibitors with Ki values of 0.7 and 1.8 microM, respectively. The present study suggests that the cellular cGMP extrusion is energized by an ATPase with a unique inhibitor profile, which clearly differentiates it from the other major classes of membrane-bound ATPases.

Urinary levels of cyclic guanosine monophosphate (cGMP) in patients with cancer of the uterine cervix: a valuable prognostic factor of clinical outcome?

Changes in urinary cyclic nucleotide levels have been reported in patients with various types of cancers. The present study was conducted to relate changes in urinary levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) to the clinical outcome of 11 patients treated for cancer of the uterine cervix. Urine was sampled for 24 h before and 3 months after primary treatment. The levels of cGMP increased in all the patients (n = 5) who relapsed within the observation period of 39 months. 4 of these patients showed an increased cGMP/cAMP ratio. In the patients without relapse (n = 6), the cGMP levels decreased, whereas the cGMP/cAMP ratios were unchanged. No marked changes in the levels of cAMP were observed for either of the groups. The measurement of urinary cGMP levels seems to be a valuable tool in the follow-up of patients with cancer of the uterine cervix.

Cyclic AMP stimulates the cyclic GMP egression pump in human erythrocytes: effects of probenecid, verapamil, progesterone, theophylline, IBMX, forskolin, and cyclic AMP on cyclic GMP uptake and association to inside-out vesicles.

The knowledge about the structure and function of the protein families responsible for cGMP synthesis and metabolic conversion has grown vastly the last years, whereas little is known about proteins that account for the cellular export of cGMP. In the present study, we have employed a model with inside-out vesicles prepared from human erythrocytes to characterize modulation and regulation of cellular cGMP extrusion. The active transport was saturable (Km of 2.4 +/- 0.2 microM, mean +/- SEM, n = 3) and coupled to ATP hydrolysis since no accumulation was detected in the presence of ATP-gamma-S and AMP-PNP. The observation that 100 microM of cAMP caused a minimal inhibition (14.4 +/- 0.3%) of active cGMP transport showed that the extrusion system for cGMP was not shared with cAMP, but a competitive interaction occurred for the ATP-independent association to the inside out vesicles. In contrast, the lowest, but physiological relevant cAMP concentrations (0.1-5 microM) stimulated the active cGMP transport with 30-35%, an observation that suggests cAMP as an allosteric regulator of the cGMP transporter. Several well-known modulators of other energy-requiring membrane transport systems caused a competitive and concentration-dependent inhibition, including verapamil (Ki = 13.0 +/- 2.4 microM), forskolin (Ki = 13.5 +/- 1.4 microM) and probenecid (Ki = 27.0 +/- 1.3 microM). Progesterone, which was the most potent inhibitor (Ki = 2.2 +/- 0.3 microM), interacted with the active cGMP transport in a noncompetitive manner. The highest concentration (100 microM) of IBMX and theophylline reduced the active cGMP uptake with 29.5 +/- 1.9% and 21.6 +/- 2.1%, respectively. None of these substances interfered with the association of cGMP to the vesicles in absence of ATP. The present results show that human erythrocytes possess a cell membrane cGMP transporter which is coupled to an ATPase. Its activity is regulated by cAMP in an apparent allosteric manner and inhibited by substances previously known to interact with other membrane transport systems.

Growth hormone increases and IGF-1 reduces the response to Escherichia coli infusion in injured pigs.

OBJECTIVE: To investigate if growth hormone (GH) or its main mediator insulin-like growth factor-1 (IGF-1) alters the response to infusion of live Escherichia coli in injured pigs. DESIGN: Controlled experiment. SETTING: University laboratory, Norway. SUBJECTS: 30 piglets. INTERVENTIONS: The response to infusion of Escherichia coli was compared after a bolus of GH 16 IU (n = 8) or a continuous infusion of IGF-1 1.3 mg/hour (n = 8) in injured piglets. A group with trauma (surgery) and Escherichia coli infusion (n = 8) and a group with trauma only (n = 6) served as controls. MAIN OUTCOME MEASURES: Systemic and regional haemodynamics, oxygen consumption, and acid-base regulation; and circulating concentrations of catecholamines, free fatty acids (FFA), glucose, and lactate Results: After infusion of Escherichia coli, cardiac output was lower and heart rate was higher in the GH than in the IGF-1-treated group. Aortic pH was lower in the GH group compared with the septic controls, whereas aortic pH was higher in the IGF-1 group compared with the septic controls. Portal vein pH was lower in the GH group than in the other three groups. Free fatty acids and lactate concentrations were higher in the GH group than in the other three groups. Glucose concentrations were lower in the IGF-1 group than in the other three groups. Renal artery flow was higher in the IGF-1 than in the GH group and the septic controls. Circulating concentrations of dopamine was higher in the IGF-1 group than in the other three groups, whereas that of noradrenaline was higher in the GH group than in the IGF-1 group. (For all differences stated, p < 0.05). CONCLUSIONS: Acute treatment with GH increased the circulatory and metabolic response to Escherichia coli infusion, in contrast to treatment with IGF-1, which reduced the response

Return of beta-adrenergic sensitivity in a patient with insulinoma after removal of the tumour.

Beta-adrenergic sensitivity and counterregulatory hormone and symptomatic responses to hypoglycaemia were studied in a 22-year-old man before and 3 and 34 weeks after removal of an insulinoma. The beta-adrenergic sensitivity was measured by the effect of an isoprenaline infusion on the heart rate, and the dose needed to increase the heart rate by 25 beats min(-1) (I25) calculated from regression lines. The glucose thresholds for the hormonal responses and symptoms were studied during a gradual fall in plasma glucose using a hypoglycaemic clamp technique. As compared with preoperative values, beta-adrenergic sensitivity was unchanged 3 weeks after surgery, but showed a marked improvement after 34 weeks, the I25 (in microg isoprenaline) being 0.96, 0.86, and 0.56, respectively. The hormone responses to hypoglycaemia were earlier, but with no improvement in symptom generation at 3 weeks. After 34 weeks, the thresholds for both hormone release and symptom generation occurred at a plasma glucose approximately 1 mmol l(-1) higher than before surgery. Thus, in our patient, there was a marked improvement in beta-adrenergic sensitivity, an earlier release of counterregulatory hormones, and an earlier recognition of hypoglycaemic symptoms after surgery. However, the restoration of these responses took more than 3 weeks.

Intrapleurally instilled mitoxantrone in metastatic pleural effusions: a phase II study.

Thirty cases (breast cancer-20 cases, malignant lymphoma-4 cases, different malignancies-6 cases) of histologically/cytologically verified malignant pleural effusion (MPE) in 29 patients were treated with intrapleurally instilled mitoxantrone (30 mg). The therapy was well tolerated. At evaluation, 25 patients had died of progressive disease. The median survival was 3 months (range 0.3-21.3 months). There were 26 responders (12 complete responses (CR), 14 partial responses (PR)), whereas 4 patients relapsed and 3 of these had an early relapse (within 3 months). Patients achieving PR or CR had a low risk (15%) of treatment failure. Five patients were subjected to a pharmacokinetic evaluation. This demonstrated rapidly declining plasma and pleural exudate levels of mitoxantrone within the first 6 hours. At 24 hours after instillation, mitoxantrone was only detected in circulating mononuclear cells. This study shows that mitoxantrone is efficacious in the treatment of MPE, and may represent a cost-effective alternative.

[How hazardous is the use of female steroid hormones?]. / Hvor farlig er bruk av kvinnelige steroidhormoner?

The development of female steroid hormone-related neoplasms such as gynaecologic and mammary cancers is influenced by hormones administered exogenously. Hormonal contraceptives and hormone replacement therapy both affect the risk of developing cancers in the endometrium, cervix, ovarium, and mammary glands. The authors refer to the recent literature and discuss the findings for the different types of cancers individually. Oestrogens promote development of cancers of the uterine corpus, but women who take progestins combined with oestrogens run no greater risk than women who do not take hormones. Female steroid hormones appear to increase the risk of developing cancer of the uterine cervix slightly, but protect against the development of ovarian cancer. An higher risk of developing mammary cancer is seen after taking oral contraceptive pills.

Export of guanosine 3',5'-cyclic monophosphate (cGMP) from human erythrocytes characterized by inside-out membrane vesicles.

The present study was undertaken to characterize the export of cGMP from human erythrocytes at 37 degrees C. Inside-out membrane vesicles were exposed to cGMP and [3H]-cGMP in the presence and absence of 2 mmol l-1 ATP. In the absence of ATP, an equilibrium was reached within 15 min for the lowest tested concentration (0.65 mumol l-1), and the amount of cGMP in the vesicles was linearly correlated to the cGMP concentrations in the incubate. These observations suggest that the ATP-independent process represents passive diffusion or non-saturated binding to membrane components. In the presence of ATP, cGMP accumulated linearly during the test period (up to 120 min) and the transport into the inside-out vesicles was dependent on both low- and high-Km transport. The kinetic parameters for the low-Km process were determined after 5 and 120 min, the Km values being 4.6 (SD 1.9) and 4.7 (SD 1.1) mumol l-1 (n = 3), respectively. The corresponding Vmax values were 400 (SD 50) and 440 (SD 70) fmol mg-1 min-1. The high-Km process was characterized by Km = 170 (SD 50) mumol-1 and Vmax = 1610 (SD 280) fmol mg-1 min-1 (n = 5). The present data demonstrate an ATP-requiring saturable transport system for cGMP in human erythrocytes.

Effect of probenecid, verapamil and progesterone on the concentration-dependent and temperature-sensitive human erythrocyte uptake and export of guanosine 3',5' cyclic monophosphate (cGMP).

Elevated extracellular cGMP levels have been observed in various clinical conditions, and the analyte has been proposed as a diagnostic marker of cardiovascular as well as malignant diseases. However, the use of extracellular cGMP as a pathophysiological marker requires detailed knowledge about the cellular biokinetics of cGMP (synthesis, metabolic conversion and export). In the present study the transport of cGMP in human erythrocytes has been further characterized. The uptake of cGMP was dependent on a concentration gradient and was temperature-sensitive, compatible with passive diffusion. The cGMP export was temperature-sensitive, saturable (Km = 3.4 +/- 1.0 mu mol l-1), inhibited by probenecid and verapamil and stimulated by progesterone. The results show that human erythrocytes possess a cGMP transport system similar to that found in other cells and that extracellular levels of cGMP are dependent on intracellular levels, membrane transport and influenced by physiological factors and pharmacological agents.

Calcifying amyloidoma of the breast.

In this case, a distinctive amyloid tumor of the breast clinically simulated carcinoma, although the patient related onset to trauma. Hepatosplenomegaly, elevated globulins, and anemia led to identification of large amounts of monoclonal IgG-kappa production. The patient died of renal failure within several months despite chemotherapy. The matrix of the breast tumor was tinctorially characteristic of amyloid light chain (AL) protein. The mass contained islands of plasma cells that morphologically suggested local production of amyloid matrix. Moreover, plasma cell and matrix immunohistochemically displayed reactivity of IgG-kappa protein, indicating a clonal plasma cell infiltrate. Pseudo-acinar arrangement of plasma cells may be misinterpreted as epithelial cells in needle biopsy specimens. The notion that some amyloidomas may represent in situ production of protein by clonal immunocytes ("secretory immunocytomas") should be further studied.

Intraosseous infusion of a small volume of hyperosmotic fluid increases mean arterial pressure and lessens the catecholamine response in pigs with haemorrhagic shock.

OBJECTIVE: To measure the plasma catecholamine concentrations during an episode of haemorrhagic shock treated by intraosseous infusion of a small volume of hyperosmotic fluid in a standardised porcine model. DESIGN: Randomised open study. SETTING: University hospital, Norway. MATERIAL: 14 piglets. INTERVENTION: Two groups of piglets (n=7 each) were anaesthetised with ketamine and bled to a mean arterial pressure of 40 mm Hg. After 30 minutes the animals were randomised to receive 100 ml of either hyperosmotic (2.4 mo/l) or iso-osmotic (0.29 mo/l) fluid (equal volumes of glucose and sodium chloride) into the tibial bone marrow. MAIN OUTCOME MEASURES: Short term (70 minutes) observation of changes in haemodynamic, biochemical and hormonal variables. RESULTS: The hyperosmotic infusion significantly improved the circulation (mean arterial pressure and cardiac index) compared with the iso-osmotic infusion (p < 0.05). The increased plasma catecholamine concentrations returned to the reference ranges 20 minutes after the hyperosmotic infusion, and were significantly different (p < 0.05) from the catecholamine concentrations observed in the iso-osmotic treatment group. CONCLUSION: Intraosseous hyperosmotic resuscitation increases the circulatory performance and reduces the plasma catecholamine concentrations during haemorrhagic shock in pigs.