Complement and contact system activation in acute congestive heart failure patients.

Recent experimental data indicate a pathogenic role of complement activation in congestive heart failure (CHF). The aim of this study was to evaluate contact and complement systems activation in patients hospitalized for an acute episode of CHF. Forty-two of 80 consecutive patients admitted at our hospital with confirmed diagnosis of acute CHF were enrolled. They underwent blood sampling within 24 h from admission (T0) and at clinical stability (T1). Patients were stratified for ejection fraction (EF) based on echocardiographic test. We measured plasma levels of C3, C4, sC5b-9 and cleaved high molecular weight kininogen (contact activation marker). At T1, C3 levels increased significantly compared to T0 (97 ± 2 versus 104 ± 3% of total pooled plasma, P < 0·01). Classifying patients according to EF, only patients with preserved EF presented a significant increase of C3 from T0 to T1 (99 ± 3 versus 108 ± 4%, P = 0·03). When the sample was stratified according to clinical outcome, C3 (98 ± 3 versus 104 ± 4%, P = 0·03) and sC5b-9 levels (204 ± 10 versus 230 ± 11 ng/ml, P = 0·03) were increased in patients who had positive outcome after hospitalization. CHF patients with preserved EF and positive outcome after hospitalization showed higher levels of sC5b-9 in the T1 period compared with T0 (211 ± 14 versus 243 ± 14 ng/ml, P = 0·04). Our results suggest that the complement system reacts differently if CHF occurs with preserved or reduced EF. This finding is interesting if we consider the difference in epidemiology, pathogenesis and possible therapeutic approaches of these two clinical entities.

Equine-derived bone substitutes in orthopedics and traumatology: authors' experience.

AIM: To evaluate the use of equine-derived bone grafts in the treatment of bone loss in a heterogeneous clinical case series. METHODS: The study population was 48 patients (29 males and 19 females; mean age, 49 years; range, 9-84); the orthopedic defect site was located on the right side in 22 and on the left side in 26 cases. The graft material was antigen-free equine-derived collagen bone cleaned with an enzymatic treatment. RESULTS: Clinical and radiographic healing times were virtually similar; graft osseointegration needed from two to three months longer to heal. CONCLUSION: The outcome after grafting with an equine-derived bone substitute was satisfactory. Further study is needed to demonstrate its statistically significant effectiveness in the treatment of orthopedic defects like those in this series.

Treatment of incomplete abortion and miscarriage with misoprostol.

A literature review was conducted to determine whether misoprostol is an effective treatment for incomplete abortion and, if so, to recommend an appropriate regimen. All English language articles published before October 2007 using misoprostol in at least one of the study arms were reviewed to determine the efficacy of misoprostol when used to treat incomplete abortion in the first trimester. All available unpublished data previously presented at international scientific meetings were also reviewed. Sufficient evidence was found in support of misoprostol as a safe and effective means of non-surgical uterine evacuation. A single dose of misoprostol 600 microg oral is recommended for treatment of incomplete abortion in women presenting with a uterine size equivalent to 12 weeks gestation.

A reliable endocrine test with human menopausal gonadotropins for diagnosis of true hermaphroditism in early infancy.

In true hermaphroditism diverse phenotypes and karyotypes are found; there are no distinctive laboratory features that can distinguish it from other intersex disorders, thus the diagnosis is made by the histological findings. Existence of Leydig cells is demonstrated by testosterone levels above the female range; however, presence of ovarian tissue cannot be ascertained because of the absence of a reliable functional test. Unless appropriate biopsies are performed or the whole gonad is removed, there is a risk of not diagnosing true hermaphroditism. To find a reliable test that can differentiate patients with true hermaphroditism from those with other intersex disorders, we investigated the estradiol (E2) response to human menopausal gonadotropins (hMG) in infants with genital ambiguity. These results were correlated with the histological findings. Eleven infants with genital ambiguity and four with a high scrotal testis were stimulated every 12 h with 2 IU/kg hMG. If E2 rose above 80 pg/mL (cut-off point), the test was discontinued; if after 7 days E2 remained below 80 pg/mL, the hMG dose was doubled and stimulation extended for 7 additional days. In five patients in whom true hermaphroditism was later histologically demonstrated, E2 rose above 80 pg/mL. In two of them, ovarian tissue was removed and hMG stimulation repeated; no response above our cut-off point was observed during the second test. The maximal E2 response to hMG in the remaining 10 individuals was 43 pg/mL; after laparotomy or gonadal biopsies no ovarian tissue was found. The hMG stimulation test can be considered a reliable and safe dynamic procedure for demonstrating the presence or absence of ovarian tissue in infants with genital ambiguity.

Relationships of plasminogen activator inhibitor-1 to anthropometry, serum insulin, triglycerides and adipose tissue fatty acids in healthy men.

Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1), responsible for reduced fibrinolytic activity, have been shown to be an important risk factor for cardiovascular disease. PAI-1 plasma levels are influenced by several factors which have not yet been fully clarified, including dietary fat intake. The relationships of PAI-1 with other cardiovascular risk factors are still not well known. In a random sample of 38-year-old healthy men (n = 94), the association of PAI-1 plasma levels (measured as activity and antigen) with anthropometric parameters, serum lipids, fasting and 2 h insulin and glucose concentration after oral glucose-load was analysed. Furthermore, the fatty acid composition of subcutaneous adipose tissue, as an objective and reliable index of dietary fat intake, was measured. The univariate analysis showed that plasma levels of PAI-1 were significantly associated with body mass index (BMI) (r = 0.37, P < 0.001), waist/hip ratio (WHR) (r = 0.26, P < 0.01), serum triglycerides (r = 0.47, P < 0.0001), HDL/total cholesterol ratio (r = -0.35, P < 0.001), fasting and 2-h insulin (r = 0.27, P < 0.01 and r = 0.34, P < 0.001) and glucose concentrations (r = 0.25, P < 0.05 and r = 0.28, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationships of blood pressure to fibrinolysis: influence of anthropometry, metabolic profile and behavioural variables.

OBJECTIVE: To investigate the relationship between blood pressure and the plasma fibrinolytic system and to verify whether this association was independent or mediated by one or more potential confounding factor. DESIGN: A random sample of 94 males aged 38 years subdivided into normotensives, hypertensives and those hypertensives with the highest blood pressure values. METHODS: Overall and regional obesity, blood lipids, fasting and 2-h post-load glucose, C-peptide and insulin levels, and main behavioural variables, including adipose tissue fatty acid composition (an objective index of dietary fat intake), were measured. The plasma fibrinolytic system was evaluated by determining activities and total plasma concentrations of both tissue-type plasminogen activator before and after venous occlusion, and its inhibitor plasminogen activator inhibitor type-1 (PAI-1). RESULTS: PAI-1 activity was significantly higher in the hypertensives than in the normotensives. PAI-1 antigen tended to parallel PAI-1 activity, and levels of tissue-type plasminogen activator antigen and activity tended to be lower in the hypertensives at baseline and after venous occlusion, but not significantly different from those in the normotensives. The hypertensives also had significantly higher body mass index and body fat content (measured by bio-impedance), increased plasma triglycerides, uric acid, fasting and 2-h glucose, C-peptide and insulin concentrations. In univariate linear regression analysis both systolic and diastolic blood pressures were found to be positively correlated with PAI-1 levels (r = 0.27, P < 0.01, for both). This correlation was maintained after adjustment for total body fat, fasting glucose, fasting insulin concentration or adipose tissue alpha-linolenic acid; however, it was no longer significant after adjustment for plasma 2-h insulin, 2-h C-peptide, 2-h glucose or triglyceride levels. Multivariate regression analysis revealed that only 2-h insulin and triglyceride concentration showed an independent association with PAI-1 levels. CONCLUSIONS: This study confirms that, in 38-year-old males, hypertension is associated with increased PAI-1 activity. It supports the possibility that the relationship between blood pressure and PAI-1 may reflect the overall effect of the insulin resistance syndrome (in particular hyperinsulinaemia and hypertriglyceridaemia) rather than a direct effect of blood pressure on the fibrinolytic system.

Selenium dependent glutathione peroxidase: a physiological regulatory system for platelet function.

In human platelets the selenoenzyme glutathione peroxidase (GSH-Px) acts as a scavenger of the peroxides generated during the burst of arachidonic acid (AA) metabolism. Such a mechanism inhibits the biosynthesis of both thromboxane A2 (TXA2) and lipoxygenase products. The same mechanism is not effective on the prostacyclin (PGI2) biosynthesis from cultured endothelial cells. In order to evaluate this effect in vivo, besides in vitro, we activated the enzyme in eight normal volunteers by increasing their daily Se intake for 8 weeks, monitoring: platelet GSH-Px activity, platelet aggregation induced by AA and U 44069, and concurrent malondialdehyde (MDA) and thromboxane B2 (TXB2) production, urinary excretion of renal and systemic TXA2 and PGI2 metabolites, platelet enzyme activities of the hexose monophosphate pathway and glutathione content, platelet adenine nucleotides, bleeding time, plasma Se concentration. We found: a) progressive platelet GSH-Px activation by Se paralleling an enhancement of platelet aggregation threshold values for AA, but not for U 44069; b) concurrent inhibition of platelet biosynthesis of TXA2 both in vitro and in vivo while the biosynthesis of systemic prostacyclin was unaffected; c) a progressive increase in the bleeding time, unmodified by aspirin. In conclusion, we believe that Se-dependent GSH-Px represents a physiological mechanism regulating the biosynthesis of prostanoids with implications in platelet function and that a Se dietary supplement might be considered in the prevention of arterial thrombosis.

Enhanced "in vitro" release of platelet alpha-granules after acute myocardial infarction (AMI).

In vivo platelet activity was studied in 58 patients with AMI on admittance to the Coronary Care Unit, in 48 of these patients after 1 week, in 30 after 1 month and in 24 patients after 6 months. Patients were carefully selected and excluded if they had associated diseases known to increase platelet activity. In vivo activation was studied by evaluating the plasma concentration of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in the same blood sample. On admittance (x = 58.5) and on day 7 (x = 52.9) beta-TG values were significantly higher than those obtained in the control group (x = 29). beta-TG values were moderately elevated after 1 month (x = 37.7) and then returned to values similar to those of the control group after 6 months (x = 27.9). The simultaneous assessment of PF4 shows a beta-TG/PF4 ratio indicative for in vitro release (less than or equal to 2.5) in many patients on days 1 and 7. Moreover, the beta-TG/PF4 ratio in patients with AMI tends towards 2 when beta-TG values are high. These results may indicate a greater tendency to an in vitro platelet release in the acute phase of AMI.

Hyperferritinaemia without iron overload: pathogenic and therapeutic implications.

It is not unusual to meet increased levels of ferritinaemia in patients apparently healthy. Among other causes of hyperferritinaemia, recently was described the Hereditary Hyperferritinemia Cataract Syndrome, a genetic condition characterized by increased serum ferritin values without iron overload and bilateral nuclear cataract, both of early onset. It has been demonstrated that single or double point mutations or deletions in the stem-loop structure of the iron regulatory element (I.R.E.) located in the 5 untranslated regions of the ferritin L-subunit gene (19q13.1) are responsible for the upregulation of ferritin. This overexpression only for the L-chain gives rise to typical piles in several tissues. When this altered ferritin accumulates in lens it causes bilateral nuclear cataracts, that is the peculiar sign of this syndrome. It is essential to differentiate true iron overload from Hereditary Hyperferritinaemia Cataract Syndrome (H.H.C.S.), because these patients rapidly develop iron deficient anaemia when venosectioned. Here we describe a case report about a 40 years old healthy female blood donor who presented isolated hyperferritinaemia without iron overload, in the absence of concomitant pathologies. Anamnestic, biochemical, instrumental and clinical investigations led us to diagnose H.H.C.S., a pathology first described in 1995. From 1995 to date about 40 cases concerning patients showing the characteristics of this syndrome from Europe, USA, and Australia were described. Biochemical, genetical and clinical investigations led finally to understand every matter of this pathology, providing conclusive and exhaustive explanations.

Plasma levels of apolipoprotein E and genetic markers in elderly patients with Alzheimer's disease.

Besides apolipoprotein E (APOE) polymorphism, whose association with Alzheimer's disease (AD) has been confirmed in most of the numerous population samples studied, other markers have been investigated. In most cases the association firstly described was not confirmed in subsequent works. Since it is important to examine these associations in as many populations as possible, we investigated APOE, APOC1, APOC2, alpha-1 antichymotrypsin (ACT) and presenilin-1 (PS-1) polymorphisms in a series of elderly patients with late-onset sporadic AD from Northern Italy and in a sex and age-matched control group. We could not confirm the significantly higher frequency of the ACT*A allele among carriers of APOE e*4 allele described elsewhere, although a similar trend was observed. The APOC2 and the PS-1 distributions were similar between patients and controls. However, we observed a significant difference in the genotype and allele frequencies of APOE and APOC1: patients had higher e*4 and C1*2 allele frequencies. This finding confirms the important role for APOE in AD occurrence. In addition, APOC1 seems to be an interesting marker because, though in strict linkage disequilibrium with APOE, it seems to play an independent role in AD risk. In contrast to previously reported data, plasma apoE concentrations were similar in patients and in controls. An interaction between APOE and APOC1 polymorphisms and apoE levels was observed in patients: subjects carrying the APOE E3/E2 or the APOC1 2-2 genotype have higher apoE concentrations than those who do not.

Use of purified dermatan sulfate for heparin cofactor II (HC II) assay.

HC II functional assays are generally preferred with respect to immunochemical assays. Nevertheless functional assays can be biased by the antithrombin III (AT III)-heparin complex activity; in fact trace amounts of heparin generally contaminate dermatan sulfate (DS) commercial preparations used as HC II reaction activators. We have employed a purified DS preparation showing these features: DS concentration 94.4%, chondroitin sulfate 5.6%, M.W. 21.4 kDa. The absence of any interference due to AT III-heparin complexes was verified in a kinetic HC II assay of some human plasma pools. The immunological inhibition of AT III by anti-AT III caused a minimal decrease (6-8%) of the reaction slope, attributable to AT III activity. Progressive increase of heparin concentration in the assay was effective only starting from 30 U/ml (the assay was carried out in the presence of polybrene to prevent any AT III activation). The reference interval (mean +/- SD) obtained from 157 normal subjects was 100.8 +/- 20.2%; there was a good correlation with immunoreactive HC II. The purified DS we have used seems suitable for routinary assays of HC II where a minimal interference due to AT III-heparin is required.

Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement.

Selenium added to the culture medium of confluent pig aortic endothelial cells caused a time-related elevation in the activity of the hydroperoxide scavenging enzyme: glutathione peroxidase. This increased activity was associated with an enhanced ability to produce prostacyclin irregardless of whether the agonist was arachidonic acid or thrombin. Since prostacyclin synthetase is believed to be irreversibly inhibited by alkyl hydroperoxides, we feel that the greater production of prostacyclin by selenium-treated cells as compared with control cells may reflect a protective effect of GSH.Px towards the synthetase enzyme. The results from this study may explain the observations made on a group of human volunteers ingesting selenium as a dietary supplement. After six weeks treatment with selenium, bleeding time in this group was prolonged suggesting an improved ability to synthesize prostacyclin as a result of selenium-dependent glutathione peroxidase activation in the vessel wall.

Serum paraoxonase activity is decreased in uremic patients.

Paraoxonase is a high-density lipoprotein (HDL)-associated enzyme capable of hydrolysing lipid peroxides. We measured the activity of serum paraoxonase together with serum concentrations of a variety of lipid constituents--total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL), cholesterol, triglycerides, apolipoproteins A-I and B--in 60 hemodialyzed (HD) patients. We found that the paraoxonase activity was significantly reduced in HD patients compared with 64 healthy controls (mean median and interquartile values: 93, 63, 87 IU/l in HD patients and 151, 120 and 135 IU/l in controls). In patients, the trimodal frequency of distribution of paraoxonase activity showed a shift toward lower levels. The effect of NaCl on enzyme activation was more pronounced in the patient group, as compared with controls, suggesting a higher frequency of the B allozyme (more responsive to NaCl) in this population. We suggest that altered HDL subfraction, present in HD patients, may be the main cause of the widespread depression of paraoxonase. Furthermore, the higher frequency of allozyme B among HD patients might increase the risk of coronary artery disease. In conclusion, paraoxonase activity may be an adjunctive index of altered lipoprotein metabolism with important repercussions on atherosclerosis.

On the mechanisms of action of short-term levonorgestrel administration in emergency contraception.

The effects of short-term administration of levonorgestrel (LNG) at different stages of the ovarian cycle on the pituitary-ovarian axis, corpus luteum function, and endometrium were investigated. Forty-five surgically sterilized women were studied during two menstrual cycles. In the second cycle, each women received two doses of 0.75 mg LNG taken 12 h apart on day 10 of the cycle (Group A), at the time of serum luteinizing hormone (LH) surge (Group B), 48 h after positive detection of urinary LH (Group C), or late follicular phase (Group D). In both cycles, transvaginal ultrasound and serum LH were performed from the detection of urinary LH until ovulation. Serum estradiol (E2) and progesterone (P(4)) were measured during the complete luteal phase. In addition, an endometrial biopsy was taken at day LH + 9. Eighty percent of participants in Group A were anovulatory, the remaining (three participants) presented significant shortness of the luteal phase with notably lower luteal P4 serum concentrations. In Groups B and C, no significant differences on either cycle length or luteal P4 and E2 serum concentrations were observed between the untreated and treated cycles. Participants in Group D had normal cycle length but significantly lower luteal P4 serum concentrations. Endometrial histology was normal in all ovulatory-treated cycles. It is suggested that interference of LNG with the mechanisms initiating the LH preovulatory surge depends on the stage of follicle development. Thus, anovulation results from disrupting the normal development and/or the hormonal activity of the growing follicle only when LNG is given preovulatory. In addition, peri- and post-ovulatory administration of LNG did not impair corpus luteum function or endometrial morphology.

Serum estrogens and ovulation return in chronic users of a once-a-month injectable contraceptive.

To determine whether the long-term exposure to a monthly injectable contraceptive, containing dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg, induces significant changes on the serum estrogens profile and ovulation return in women, a study in chronic users was undertaken. Ovarian function was assessed for 3 months following a single injection of the contraceptive agent in a group of women (n = 7) who have been on this formulation for an average period of 6.7 years and in a non-user control group (n = 7). The serum concentrations of 17 beta-estradiol, estrone and progesterone were measured in samples drawn at regular intervals throughout the entire study. The endometrial bleeding pattern was recorded in all subjects. The results indicated that the post-injection serum estradiol maximum levels (exogenous peak) occurred significantly earlier (p less than 0.05) in chronic users as compared with the non-user control group. Baseline serum estrone concentrations were slightly higher in chronic users than those observed in the control group, while the values of serum 17 beta-estradiol did not exhibit significant differences among the two groups. Ovulation was documented within 60-90 days after injection in all subjects from both groups. A similar length of the first bleeding-free period was observed in all participants. The overall data provide evidence of a moderate increase of estrone, one of the still active metabolic conversion products of 17 beta-estradiol, in the sera of chronic users of this combined contraceptive without affecting its pharmacodynamics.

PIP: The effects of longterm exposure to a monthly injectable contraceptive agent containing 150 mg of dihydroxy-progesterone acetophenide and 10 mg of estradiol enanthate on the serum estrogens profile and ovulation return were investigated in 7 women who had been taking this form of fertility control for an average of 6.7 years and 7 previous nonuser controls. Blood samples were taken immediately prior to injection and twice a week thereafter for a total of 3 months. Longterm users were injected 25-30 days after their previous injection, while the nonusers were injected during the early follicular phase of their menstrual cycle. Baseline serum estradiol concentrations were not significantly different between the 2 groups; immediately after injection, however, serum levels of estradiol increased rapidly to attain a maximum value of 314 in longterm users and 283 pg/ml in controls. The time required to reach maximum estradiol levels was significantly less in longterm users (4.2 days) compared with controls (6.3 days). Higher serum estrone levels were recorded at baseline in the chronically exposed women, although there were no significant differences between groups after 30 days. Ovulation was documented 60-90 days after injection in all subjects and endometrial bleeding patterns were the same in both groups. Overall, these data suggest that the slight increase in serum estrone levels associated with longterm use of this injectable contraceptive is not sufficient to produce prolonged ovarian and endometrial function impairment.

Pharmacodynamic assessment of dihydroxyprogesterone acetophenide plus estradiol enanthate as a monthly injectable contraceptive.

The pharmacodynamics of the combination of dihydroxyprogesterone acetophenide (DHPA) and estradiol enanthate (E2-EN) following its intramuscular administration at two doses were studied in 16 healthy women of reproductive age. Subjects were randomly allocated in two groups: group I (n = 9) received the combination DHPA 150 mg + E2-EN 10 mg on three consecutive monthly injections, while group II (n = 7) received half-dose of the same formulation. Ovarian function and endometrial bleeding patterns were investigated in all participants for one pre-treatment cycle, three treatment intervals and two post-treatment cycles. The results disclosed that ovulation was inhibited for at least 30 days following DHPA/E2-EN administration in all participants from both groups. The circulating estradiol levels 30 days after last injection were slightly elevated as compared with those observed in normal early follicular phase. Return to ovulatory cycles was documented within 90 days after treatment. The length of the bleeding-free intervals during treatment was shortened in both groups, particularly in group II. No significant changes in HDL-cholesterol levels were observed throughout the study. It is envisaged however, that large modification of the formulation and additional long-term safety studies will be required prior to its recommendation.

PIP: The pharmacodynamics of the combination of dihyroxyprogesterone acetophenide (DHPA) and estradiol enanthate (E2-EN) following its intramuscular administration at 2 doses were studied in 16 healthy women of reproductive age attending the Family Planning Clinic at General Hospital in Mexico City. Subjects were randomly allocated in 2 groups: group I (n=9) received the combination DHPA 150 milligrams and E2-EN 10 milligrams on 3 consecutive monthly injections, while group II (n=7) received 1/2 dose of the same formulation. Ovarian function and endometrial bleeding patterns were investigated in all participants for 1 pretreatment cycle, 3 treatment intervals and 2 post-treatment cycles. The results disclosed that ovulation was inhibited for at least 30 days following DHPA/E2-EN administration in all participants from both groups. The circulating estradiol levels 30 days after last injection were slightly elevated as compared with those observed in normal early follicular phase. Return to ovulatory cycles was documented within 90 days after treatment. The length of the bleeding-free intervals during treatment was shortened in both groups, particularly group II. No significant changes in HDL-cholesterol levels were observed throughout the study. It is envisaged however, that large modification of the formulation and additional long-term safety studies will be required prior to its recommendation.

Emergency contraception in Mexico City: what do health care providers and potential users know and think about it?

Emergency contraception promises to reduce Mexico's high unwanted pregnancy and unsafe abortion rates. Because oral contraceptives are sold over-the-counter, several emergency contraceptive regimens are already potentially available to those women who know about the method. Soon, specially packaged emergency contraceptives may also arrive in Mexico. To initiate campaigns promoting emergency contraception, we interviewed health care providers and clients at health clinics in Mexico City, ascertaining knowledge, attitudes, and practices concerning the method. We found limited knowledge, but nevertheless cautious support for emergency contraception in Mexico. Health care providers and clients greatly overestimated the negative health effects of emergency contraception, although clients overwhelmingly reported that they would use or recommend it if needed. Although providers typically advocated medically controlled distribution, clients believed emergency contraception should be more widely available, including in schools and vending machines with information prevalent in the mass media and elsewhere.

PIP: An interview was conducted to ascertain knowledge, attitudes, and practices concerning emergency contraception (EC) among health care providers and potential EC users in metropolitan Mexico. Findings showed that there was a limited knowledge about EC per se and its method, but nevertheless, most of the participants were cautious to support EC in Mexico. Health care providers and clients greatly overestimated the negative health effects of EC, although clients overwhelmingly reported that they would use or recommend it if needed. Although providers typically advocated medically controlled distribution, clients believe EC should be more widely available, including in schools and vending machines, with information prevalent in the mass media and elsewhere.

Effects of acetate on glucose metabolism and cellular ATP content during hemodialysis.

In view of multiple interactions of acetate with intermediary metabolism, we studied the effects of the exogenous acetate load during dialysis on glucose and energy metabolism. IV glucose tolerance test (glucose 0.33 g/kg BW) and platelet ATP content were evaluated in 16 patients before and after a single hemodialysis session with acetate 38 mEq/l in the dialysate. IV glucose tolerance was greatly impaired in all patients after hemodialysis (K: 1.08 +/- 0.30 vs predialysis value of 2.05 +/- 0.85, p less than 0.001). Platelet ATP content was unchanged by dialysis (3.74 +/- 1.02 mumol/10(11) PLTs before and 3.55 +/- 0.69 mumol/10(11) PLTs after), however, individual variations in platelet ATP content ranged from +32 to -31% of the initial values. Postdialysis plasma acetate levels ranged from 1.5 to 9.2 mmol/l and were inversely correlated with postdialysis glucose tolerance test (r: -0.61, p less than 0.01) and platelet ATP content variations (r: -0.51, p less than 0.05). Our study demonstrates that glucose utilization is acutely impaired by acetate dialysis and suggests that the reduced glycolytic activity may be due to a negative feed-back mechanism in the presence of exogenous fuel. It also demonstrates a great variability in platelet ATP content following hemodialysis, which probably depends on the different patients' ability to oxidize acetate.

Studies on gonadal dysgenesis: variable expressivity of the XY testicular dysgenesis syndrome; two case reports.

Two adult unrelated XY phenotypically female individuals with sexual infantilism and genital ambiguity were studied. Mosaicism was ruled out by the assessment of a normal 46,XY karyotype in four different cell lines. Persistently elevated LH and FSH serum levels with concomitant normal pituitary Gn-RH responsiveness were found. Baseline serum testosterone concentrations were low, but they exhibited a slight though significant rise following HCG stimulation. Surgical and histological findings included the presence of Mullerian and Wolffian derivatives and small bilateral dysgenetic testes with absence of germ cell epithelium, scarce Sertoli cells, and hyperplastic Leydig cells. The overall data indicated an anatomo-functional testicular impairment particularly confined to the tubular compartment. By comparing the clinical and endocrine features of this incomplete form of the XY testicular dysgenesis with the complete and other unusual forms, further evidence is provided of a wide heterogeneity of the syndrome, and a more detailed classification is proposed.