Procalcitonin, C-reactive protein, white blood cells and SOFA score in ICU: diagnosis and monitoring of sepsis.

AIM: To determine in critically ill patients the value of procalcitonin (PCT), C-reactive protein (CRP), sequential organ failure assessment (SOFA) score and white blood cell count in diagnosis and monitoring of sepsis. METHODS: Patients admitted to a medicosurgical intensive care unit in a prospective, observational study, were observed consecutively. According to ACCP/SCCM Consensus Conference definition were defined 4 groups: SEPSIS/SS (sepsis, severe sepsis, septic shock), SIRS, No-SIRS and TRAUMA. RESULTS: Two hundred and fifty five clinical events on a total of 1 826 observation days were observed: 111 SEPSIS/SS, 49 TRAUMA, 45 SIRS and 50 No-SIRS. ROC values, in the diagnosis of sepsis, were 0.88 for PCT, 0.74 for CRP, 0.8 for Sepsis score, 0.74 for SOFA, 0.62 for neu-throphils granulocytes (p<0.05). The best cut-off values in the diagnosis of sepsis were 0.47 ng/mL for PCT and 128 mg/L for CRP. PCT and SOFA were higher in septic shock than in severe sepsis and sepsis (p<0.05 in all cases). The maximum CRP level in SEPSIS/SS was reached only after 24-48 h of observation. Admission PCT value of TRAUMA patients whom evolving in septic complication was higher than patients with a favourable course: 3.4 ng/mL (range 2.63-12.71) vs 1.2 ng/mL (range 0.5-5.2) (p<0.05). TRAUMA patients with septic complications present an early and quick significant increase of PCT (p<0.05). CONCLUSIONS: PCT and CRP may be useful together with bacteriological data in sepsis diagnosis; PCT and SOFA closer correlate with the infection severity; PCT is the better parameter to estimate severity, prognosis or further course of the disease.

Elevated plasma levels of factor VIII in women with early recurrent miscarriage.

AIMS: Inherited and acquired thrombophilia have been found to be associated with recurrent pregnancy loss. This paper examines whether or not elevated factor (F)VIII:C plasma levels, which have been demonstrated to be an independent risk factor for venous thromboembolism, are a risk factor for early recurrent miscarriages also. PATIENTS AND METHODS: Consecutive women referred to our clinic with a history of early recurrent abortion (at least three pregnancy losses before week 13 of gestation) were eligible for the study. Exclusion criteria were endocrine, immunological, anatomical and genetic causes of embryo demise, as well as any thrombophilic abnormality, either congenital or acquired, or a personal or familial history of venous thromboembolism. FVIII:C plasma levels were determined in 51 cases and in 51 controls matched for age, ethnicity and blood group. RESULTS: The mean FVIII:C level in the control subjects was 106.8 IU dL-1, compared with 128.2 IU dL-1 in the patients group (P = 0.0002). Thirteen (25.5%) of the 51 patients had FVIII:C values exceeding the 90th centile of the control population (145 IU dL-1), compared with four subjects in the control group (chi2 = 4.52; P = 0.033; odds ratio = 4.02, 95% confidence interval 1.09, 16.05). No cases with increase in FVIII:C levels attributable to an acute-phase reaction, as assessed by C-reactive protein plasma concentration, were found. CONCLUSIONS: We found FVIII:C levels significantly higher in women with early recurrent miscarriage compared with controls. This finding suggests a possible association between this thrombophilic condition and early reproductive failures.

A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial.

Primary dysmenorrhea is a syndrome characterized by painful uterine contractility caused by a hypersecretion of endometrial prostaglandins; non-steroidal anti-inflammatory drugs are the first choice for its treatment. However, in vivo and in vitro studies have demonstrated that myometrial cells are also targets of the relaxant effects of nitric oxide (NO). The aim of the present study was to determine the efficacy of glyceryl trinitrate (GTN), an NO donor, in the resolution of primary dysmenorrhea in comparison with diclofenac (DCF). A total of 24 patients with the diagnosis of severe primary dysmenorrhea were studied during two consecutive menstrual cycles. In an open, cross-over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first days of menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses/day of 50 mg DCF or 2.5 mg/24 h transdermal GTN for the first 3 days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side-effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on the first day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable. Both treatments significantly reduced DPI by the 30th minute (GTN, -12.8 +/- 17.9; DCF, -18.9 +/- 16.6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher than those for DFC (after one hour: GTN, -12.8 +/- 17.9; DFC, -18.9 +/- 16.6 and after two hours: GTN, -23.7 +/- 20.5; DFC, -59.7 +/- 17.9, p = 0.0001). Low back pain was also relieved by both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache--attributed to its use--became intolerable. These findings indicate that GTN has a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea.

Hypothalamic resetting at puberty and the sexual dimorphism of migraine.

It is well known that migraine is far more represented in females than in males. However, this gender-related difference is present only during reproductive life since in prepubertal children, migraine prevalence figures are independent of sex. Thus, transition to puberty accounts for changes which render females more susceptible to migraine attacks. In females, the main driver of the hormonal events allowing sexual maturation is the pulsatile secretion of hypothalamic LHRH modulated by opioid activity. Clinical reports suggest that migraine attacks could be prevented by the abolition of this neurohormonal secretion. On the other hand, several clinical and experimental observations have focused on neuroendocrine systems (opiatergic, serotonergic, adrenergic) as participating in the constitution of the so-called "migraine trait", the biological predisposition in patients that would explain their sensitivity to migraine triggers. Such neuroendocrine secretions are mainly dependent upon hypothalamic activity where a sexual dimorphic nucleus has been discovered in the preoptic area. We suggest that the sexual dimorphism of migraine should be sought in hypothalamic networks related to LHRH secretion.

Pulsatile secretion of ACTH and cortisol in premenopausal women: effect of obesity and body fat distribution.

OBJECTIVE: There is emerging evidence that women with visceral obesity may have hyper-responsiveness of the hypothalamic-pituitary-adrenal axis. There are no studies on basal daily secretory pattern of ACTH and cortisol in subjects with different obesity phenotypes. DESIGN AND PATIENTS: In this study we examined daytime pulsatile secretion of ACTH and cortisol in two groups of premenopausal obese women with visceral (V-BFD) (BMI 37.1 +/- 1.7) and subcutaneous (S-BFD) (BMI 38.8 +/- 1.5) body fat distribution (measured by CT scan) and in a group of normal weight healthy controls (BMI 21.1 +/- 0.5). After an overnight fast, blood samples were taken at 15-minute intervals for 12 h (49 samples, from 0800 h until 2000 h). All women avoided breakfast but had a normal lunch and dinner, both containing similar food, energy and nutrient composition. ACTH and cortisol responses to mixed meals at noon and in the evening were also investigated. RESULTS: Mean values of ACTH and cortisol did not differ between the groups. However, ACTH pulse frequency was significantly higher in V-BFD (P < 0.06) and S-BFD (P < 0.02) obese women than in controls, without any significant differences between the two obese subgroups. Mean ACTH pulse amplitude was lower in the V-BFD than in S-BFD obese (P < 0.02) and control (P < 0.05) groups. Cortisol episodic characteristics did not differ between V-BFD and S-BFD obese and controls. All differences in ACTH pulsatile parameters between obese and controls and between the two obese subgroups were evident only in the morning, with no further significant differences during the early and late afternoon. There were no significant differences in cortisol parameters during the three periods of the day between the various groups, apart from late afternoon cortisol pulse frequencies, which were significantly lower in V-BFD than in controls. After lunch, ACTH and cortisol levels significantly increased in all groups, but the cortisol increase tended to be more rapid in V-BFD than in the other two groups. After dinner, ACTH significantly increased in V-BFD and controls but not in the S-BFD group, whereas cortisol rose significantly in all groups, but significantly less in S-BFD than in V-BFD and controls. CortisolAUC (but not ACTHAUC) after lunch was significantly higher than after dinner in all groups. ACTH response after each meal was similar in all groups, but cortisolAUC after dinner was significantly lower in S-BFD than in V-BFD women. CONCLUSION: This study demonstrates that in premenopausal women, obesity, particularly the visceral phenotype, is associated with several abnormalities of ACTH pulsatile secretion, particularly in the morning. On the contrary, no major differences were present in either blood concentrations, diurnal rhythm or secretory pattern of cortisol between obese and controls. The responses to meals seem to indicate a much more rapid cortisol response after lunch in women with visceral obesity and a reduced activation of the hypothalamic-pituitary-adrenal axis after dinner in women with subcutaneous obesity.

Increased anticardiolipin antibodies are positively related to the uterine artery pulsatility index in unexplained infertility.

The objective of the study was to evaluate, in patients with unexplained infertilty, the possible relationship between anticardiolipin antibodies and indices of uterine artery Doppler measurements. A total of 46 infertile women participated in the study and underwent ovarian stimulation. Transvaginal ultrasonography and colour Doppler were performed on the day of embryo transfer and patients were divided on the basis of pulsatility index (PI): group I, PI <2.5; group II, PI 2.5-3.0; and group III, PI >3.0. On the same day that Doppler analysis took place, peripheral blood was obtained and circulating anticardiolipin antibodies were assayed. The response to ovarian stimulation was similar in the three studied groups. No significant differences in oestradiol and ultrasonographic parameters were observed between the groups. A significant increase in anticardiolipin antibodies was observed in those patients with higher resistance to flow at the level of the uterine artery. A significant relationship was found between the uterine artery PI and anticardiolipin immunoglobulin G class (F = 14.35; P = 0.001), and immunoglobulin M class (F = 5.88; P = 0.020). It is concluded that, in unexplained infertility, anticardiolipin antibodies may be involved in uterine vascular modifications and that Doppler flow analysis of uterine arteries may be an important tool in the assessment and management of ovarian stimulation.

Difference of LH and FSH secretory characteristics and degree of concordance between postmenopausal and aging women.

OBJECTIVE: Several neuroendocrine changes occur at menopause and the present study aimed to verify whether the episodic release and the degree of concordance of LH and FSH differs between early and late postmenopausal women. METHODS: Postmenopausal (n = 32) women were enrolled and subdivided in two groups according to the menopausal age: group A (n = 22), patients with more than 2 but less than 5 years from the occurrence of menopause; group B (n = 10), patients with more than 15 years from the occurrence of menopause. All subjects underwent a pulsatility study (4 h, sampling every 10 min) to assess LH and FSH secretory characteristics and their degree of concordance. RESULTS: Mean +/- S.E.M. LH and FSH plasma levels were lower in older women than in postmenopausal women (P < 0.01). The secretory pattern was pulsatile for both LH and FSH and their pulse amplitudes were lower in aged women (P < 0.01). No significant difference was observed in terms of pulse frequency between the two groups. LH and FSH pulses were co-secreted in early postmenopausal women while such a concordance was lost in older women. CONCLUSIONS: Late postmenopause is characterized by the reduction of the amplitude of gonadotropin pulses in comparison to women in early postmenopause, reflecting changes of both GnRH secretion and/or pituitary responsiveness to GnRH. The age-related loss of concordance between LH and FSH pulses discloses the existence of a hidden FSH stimulating system, which drives FSH episodic release independently and more promptly than GnRH.

Paracoccidioidomycosis associated with acquired immunodeficiency syndrome. Report of seven cases.

We report the clinical findings and evolution of seven patients (five men and two women), the majority of them intravenous drug users, with paracoccidioidomycosis associated to acquired immunodeficiency syndrome (AIDS). In four of the patients the paracoccidioidomycosis was restricted to the lung and in the three others was generalized with cutaneous involvement. Only two of them had lived recently in rural area, an indication of the possible reactivation of latent focal infection in the other five patients. The recognition of the role of cell-mediated immunity in host defense against Paracoccidioides brasiliensis leds to the prediction of a growing occurrence of the paracoccidioidomycosis-AIDS association in areas that are endemic for these diseases.

Human envenomations due to snakebites in Marilia, State of Säo Paulo, Brazil. A retrospective epidemiological study

Eighty-four patients bitten by venomous snakes were studied retrospectively at the School of Medicine of Marília from January 1990 to August 1994. The majority of these patients were rural workers, 65 (77.38 per cent] males and 19 (22.62 per cent) females, aged eight to seventy-five. Forty-three (51.19 per cent) patients were diagnosed as having been bitten by snakes of the genus Bothrops and 41 (48.81 per cent) by Crotalus. Fifty-eight patients (69.04 per cent ) were bitten in the legs and 26 (30.96 per cent ) in the arms. January, March, April and November were the months of higher incidence of bothropic envenomations, while crotalic envenomations were not recorded only in August and September. This study showed that the prevalence of crotalic envenomations in Marília was higher than that of any other regions in Brazil. Further prospective epidemiological studies are needed for a better understanding of these findings.