Evaluation of the efficacy and safety of dilevalol in the treatment of essential arterial hypertension

Dilevalol, an optical isomer of labetalol, combines beta-blocking and vasodilator actions which prevent reflex tachycardia and it also has intrinsic beta-2-agonist action. Its low alpha-blocking action prevents orthostatic hypotension and improves first dose tolerance. The present study evaluates the efficacy and safety of dilevalol comparing it with captopril and nifedipine. Fifty-eight mild to moderate essential hypertensive patients were studied. After a 2 to 3 week placebo lead-in phase, patients with diastolic blood pressure between 95 and 105 mmHg were included., Patients were randomly assigned to one of the 3 study drugs for a 4-week period. Initially, 15 patients received dilevalol 200 mg qd and 15 captopril 100 mg bid; afterwards, 14 received dilevalol 200 mg qd and 14 nifedipine 40 mg bid. In the first group dilevalol decreased mean blood pressure (MBP) from 118.0 +/- 1.3 to 107.3 +/- 2.7 mmHg at week 4 and captopril from 117.8 +/- 1.2 to 108.6 +/- 2.7 (p less than 0.05). When dilevalol and nifedipine were compared, the former decreased MBP from 116.0 +/- 2.0 to 104.3 +/- 3.2 mmHg and the latter from 115.0 +/- 1.4 to 106.0 +/- 3.0 (p less than 0.05). The drug was well tolerated without evidence of orthostatic hypotension. Our results demonstrate that dilevalol is as safe and effective as captopril and nifedipine for the treatment of essential hypertension.     

Effects of the opiate agonist loperamide on pituitary-adrenal function in patients with suspected hypercortisolism

In the present work the possible use of loperamide, an opiate agonist, in the dynamic evaluation of patients with suspected hypercortisolism was investigated. The effects of loperamide on plasma ACTH and cortisol levels were evaluated in normal subjects and in 58 patients with suspected Cushing's syndrome. The results were compared to those obtained after the overnight dexamethasone suppression test. In normal subjects plasma ACTH and cortisol levels were significantly (p less than 0.005) suppressed by both loperamide (16 mg po) and dexamethasone (1 mg po). In 17 patients, in whom the diagnosis of Cushing's syndrome was confirmed by subsequent investigations, neither loperamide or dexamethasone inhibited cortisol (from a baseline of 606 +/- 55 nmol/L) to a nadir of 502 +/- 43 nmol/L and 539 +/- 50 nmol/L, respectively) and ACTH concentration (from a basal level of 70.1 +/- 11.8 pg/ml to a nadir of 46.0 +/- 8.6 pg/ml and 54.3 +/- 7.5 pg/ml, respectively). In 34 patients, in whom the suspect of hypercortisolism was ruled out, either loperamide or dexamethasone suppressed the pituitary-adrenal axis: cortisol and ACTH levels significantly fell from 417 +/- 24 nmol/L and 28.3 +/- 3.5 pg/ml to 60 +/- 6 nmol/L and 14.4 +/- 1.4 pg/ml after loperamide and to 26 +/- 4 nmol and 16.4 +/- 1.7 pg/ml after dexamethasone. In 7 patients discordant responses were observed. In 3 patients treated with antiepileptic drugs ACTH and cortisol levels were inhibited by loperamide, but not by dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)     

The silent corticotropinoma: is clinical diagnosis possible?

Up to now, the diagnosis of silent corticotroph cell pituitary adenomas has been made only on histopathological basis. In this paper we describe 6 women affected with pituitary adenomas, without evident clinical features of hypercortisolism, in whom retrospective data suggested the possibility of clinically diagnosing silent corticotropinomas in vivo. In all patients basal ACTH and cortisol levels were normal, and the low-dose dexamethasone test constantly suppressed serum cortisol and urinary 17-hydroxycorticosteroid levels. The CRH and/or lysine-vasopressin tests, performed in five patients, always induced exaggerated ACTH/cortisol rises. In three cases the response to the opiate agonist loperamide was assessed and no inhibition of ACTH/cortisol levels was found. All patients underwent pituitary surgery. In five cases evidence of corticotropinoma was obtained by immunohistochemistry or immunofluorescence studies; moreover, in one adenoma ACTH was secreted into the culture medium, and in another one CRH and arginine-vasopressin induced a marked intracellular [Ca++] rise. Electron microscopy study of the adenoma, removed from three patients, showed the presence of adenomatous corticotroph cells. Finally, in another woman no hormonal abnormalities were initially observed and she was operated for a "nonfunctioning" pituitary adenoma, but four years later an overt Cushing's disease appeared, suggesting that a silent corticotropinoma subsequently became functional, although the formation of a different adenoma cannot be excluded. In conclusion, the occurrence of ACTH/cortisol hyperresponsiveness to CRH and/or lysine-vasopressin and the lack of suppression of ACTH/cortisol secretion to opioid agonists in patients with apparently "nonfunctioning" pituitary tumors might allow the in vivo recognition of silent corticotropinomas.     

Prospective Study Examining Clinical Outcomes Associated with a Negative Pressure Wound Therapy System and Barker’s Vacuum Packing Technique

Background

The open abdomen has become a common procedure in the management of complex abdominal problems and has improved patient survival. The method of temporary abdominal closure (TAC) may play a role in patient outcome.

Methods

A prospective, observational, open-label study was performed to evaluate two TAC techniques in surgical and trauma patients requiring open abdomen management: Barker’s vacuum-packing technique (BVPT) and the ABThera^TM open abdomen negative pressure therapy system (NPWT). Study endpoints were days to and rate of 30-day primary fascial closure (PFC) and 30-day all-cause mortality.

Results

Altogether, 280 patients were enrolled from 20 study sites. Among them, 168 patients underwent at least 48 hours of consistent TAC therapy (111 NPWT, 57 BVPT). The two study groups were well matched demographically. Median days to PFC were 9 days for NPWT versus 12 days for BVPT (p = 0.12). The 30-day PFC rate was 69 % for NPWT and 51 % for BVPT (p = 0.03). The 30-day all-cause mortality was 14 % for NPWT and 30 % for BVPT (p = 0.01). Multivariate logistic regression analysis identified that patients treated with NPWT were significantly more likely to survive than the BVPT patients [odds ratio 3.17 (95 % confidence interval 1.22–8.26); p = 0.02] after controlling for age, severity of illness, and cumulative fluid administration.

Conclusions

Active NPWT is associated with significantly higher 30-day PFC rates and lower 30-day all-cause mortality among patients who require an open abdomen for at least 48 h during treatment for critical illness.     

The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells

In this study, we explored whether thrombopoietin (Tpo) has a direct in vitro effect on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC). We previously reported a cell separation method that uses the fluorescence-activated cell sorter selection of low Hoescht 33342/low Rhodamine 123 (low Ho/low Rh) fluorescence cell fractions that are highly enriched for LTR-HSC and can reconstitute lethally irradiated recipients with fewer than 20 cells. Low Ho/low Rh cells clone with high proliferative potential in vitro in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6 (90% to 100% HPP-CFC). Tpo alone did not induce proliferation of these low Ho/low Rh cells. However, in combination with SCF or IL-3, Tpo had several synergistic effects on cell proliferation. When Tpo was added to single growth factors (either SCF or IL-3 or the combination of both), the time required for the first cell division of low Ho/low Rh cells was significantly shortened and their cloning efficiency increased substantially. Moreover, the subsequent clonal expansion at the early time points of culture was significantly augmented by Tpo. Low Ho/low Rh cells, when assayed in agar directly after sorting, did not form megakaryocyte colonies in any growth condition tested. Several days of culture in the presence of multiple cytokines were required to obtain colony-forming units-megakaryocyte (CFU-Mk). In contrast, more differentiated, low Ho/high Rh cells, previously shown to contain short- term repopulating hematopoietic stem cells (STR-HSC), were able to form megakaryocyte colonies in agar when cultured in Tpo alone directly after sorting. These data establish that Tpo acts directly on primitive hematopoietic stem cells selected using the Ho/Rh method, but this effect is dependent on the presence of pluripotent cytokines. These cells subsequently differentiate into CFU-Mk, which are capable of responding to Tpo alone. Together with the results of previous reports of its effects on erythroid progenitors, these results suggest that the effects of Tpo on hematopoiesis are greater than initially anticipated.     

Hypertension in dialysis and kidney transplant patients

For the first time, the Canadian Hypertension Education Program has studied the evidence supporting blood pressure control in people requiring renal replacement therapy for end-stage kidney disease, including those on dialysis and with renal transplants. According to the Canadian Organ Replacement Registry’s 2008 annual report, there were an estimated 33,832 people with end-stage renal disease in Canada at the end of 2006, an increase of 69.7% since 1997. Of these, 20,465 were on dialysis and 13,367 were living with a functioning kidney transplant. Thus, it is becoming more likely that primary care practitioners will be helping to care for these complex patients. With the lack of large controlled clinical trials, the consensus recommendation based on interpretation of the existing literature is that blood pressure should be lowered to below 140/90 mmHg in hypertensive patients on renal replacement therapy and to below 130/80 mmHg for renal transplant patients with diabetes or chronic kidney disease.     

Adolescents with type 1 diabetes and risky behaviour

Aim: The aim of the student is to assess whether adolescents with type 1 diabetes mellitus (T1DM) in Italy differ from their healthy peers in regard to risky behaviour. Methods: Data were collected from 215 patients, aged 14 ± 2 years with a mean disease duration of 7 ± 5 years. The control group was comprised of 464 healthy adolescents recruited among high school students. Each patient completed an anonymous confidential questionnaire to determine the prevalence of sexual behaviour, alcohol and tobacco consumption, illicit drug use, and, among patients with diabetes and frequency of mismanagement related to diabetes care. Results: Compared with controls, subjects with diabetes showed a similar rate of sexual intercourse among males and lower rates among females (34.8% vs 35.5%, p NS and 29.4% vs 41.4%, p < 0.05, respectively). Males in the diabetes group reported a higher rate of tobacco use, whereas females showed similar or higher rates of use for every illicit drug studied. Among patients with diabetes, those who are engaged in risky behaviour showed a higher rate of treatment mismanagement (76% vs 34%, p < 0.01). Conclusion: Adolescents with T1DM are as likely as their healthy peers to engage in risky behaviour, indicating the potential benefit of anticipatory guidance concerning glycaemic control and increased risk of acute and chronic complications.     

Oligosaccharides in human milk during different phases of lactation

Twenty-one oligosaccharides of human milk were quantified by high-performance anion-exchange chromatography. Milk samples were collected from 18 mothers during the first 3 mo of lactation. The data show that the highest amount of all oligosaccharides is present at day 4 postpartum (20 g l⁻¹) and then decreases by about 20% at day 30 of lactation. The protective role played by these substances against different infectious agents, in different organs and systems of the breastfed baby, is emphasized.     

Persistent systemic inflammatory response syndrome is predictive of nosocomial infection in trauma

BACKGROUND: Admission systemic inflammatory response syndrome (SIRS) score has been previously reported to be an accurate predictor of infection and outcome in trauma. However, these data were limited to only one SIRS score at admission. A prior study in surgical intensive care unit (ICU) patients reported that the SIRS score on ICU day 2 declined after completion of resuscitation, and was a more accurate predictor of outcome. Our objective in this follow-up study was to prospectively evaluate the utility of daily SIRS scores in prediction of nosocomial infection and outcome in high-risk trauma patients. METHODS: Prospective data were collected on 702 consecutive trauma patients admitted over a 12-month period to the ICU. SIRS scores were calculated daily. Centers for Disease Control and Prevention guidelines were used for the diagnosis of infection. Multivariate linear regression was used for statistical analysis. RESULTS: Five hundred seventy-three (82%) patients sustained blunt injuries and 129 (18%) sustained penetrating injuries. The mean age was 43 +/- 21 years, with an overall mortality of 11.4%. Two hundred ninety (41.3%) of the study patients acquired a nosocomial infection (respiratory site most common), with an associated mortality rate of 12.4%. SIRS (defined as SIRS score >/= 2) on hospital days 3 through 7 was a significant predictor of nosocomial infection and hospital length of stay. Persistent SIRS to hospital day 7 was associated with a significant risk for increased mortality (relative risk, 4.7; 95% confidence interval, 1.41-12.87; p = 0.047). CONCLUSION: Persistent SIRS is predictive of nosocomial infection in trauma. Daily monitoring of SIRS scores is easily accomplished and should be considered in all high-risk trauma patients. Persistent SIRS in trauma should initiate early diagnostic interventions for determination of source of infection, and consideration of early empiric antimicrobial therapy.     

Pulmonary blastoma after liver transplant: a case report

There is an increased risk of cancer after organ transplantation mainly due to the immunosuppressive therapy required in these patients. We report a case of biphasic pulmonary blastoma in an adult male who underwent liver transplant for hepatocellular carcinoma in March 1999, followed by immunosuppressive treatment and adjuvant chemotherapy with epirubicin. Disease-free survival lasted 18 months, then a diagnosis of biphasic pulmonary blastoma was made and the patient underwent a lung lobectomy. Five months after surgical resection a recurrence of this rare tumor was recorded and two cycles of cisplatin + etoposide and ifosfamide + etoposide and one cycle of second-line chemotherapy with vinorelbine were administered. The tolerability and the efficacy of this treatment were poor. The patient died less than one year after diagnosis. To our knowledge this is the first reported case of pulmonary blastoma in a transplant patient. Our findings confirm that organ transplant recipients deserve long-term medical surveillance also in the absence of graft complications, and that pulmonary blastoma is an aggressive tumor with a poor prognosis.