Factors predictive of relapse in adult bacterial osteomyelitis of long bones.

BACKGROUND: Osteomyelitis is a difficult-to-cure infection with a high relapse rate despite combined medical and surgical therapies. Some severity factors, duration of antimicrobial therapy and type of surgical procedure might influence osteomyelitis relapse. METHODS: 116 patients with osteomyelitis were followed for ≥1 year after hospital discharge. Demographic, microbiological and clinical data, eight severity factors and treatment (surgical and antibiotic) were analyzed. RESULTS: Mean age was 53 years and 74.1% were men. Tibia (62.1%) and S. aureus (58.5%) were the most commonly involved bone and bacteria, respectively. Mean follow-up was 67.1 months. Forty-six patients underwent bone debridement, 61 debridement plus flap coverage and 9 antimicrobial therapy only. Twenty-six patients (22.4%) relapsed, at a mean of 11.2 months since hospital discharge. Duration > 3 months (p = 0.025), number of severity factors (P = 0.02) and absence of surgery (P = 0.004) were associated with osteomyelitis relapse in the univariate analysis. In the Cox regression analysis, osteomyelitis duration > 3 months (P = 0.012), bone exposure (P = 0.0003) and type of surgery (P < 0.0001) were associated with relapse. Regarding the surgical modalities, bone debridement with muscle flap was associated with better osteomyelitis outcomes, as compared with no surgery (P < 0.0001) and debridement only (P = 0.004). CONCLUSIONS: Osteomyelitis extending for > 3 months, bone exposure and treatment other than surgical debridement with muscular flap are risk factors for osteomyelitis relapse.

Trends in the dispensation of antidepressant drugs over the past decade (2000-2010) in Andalusia, Spain.

PURPOSE: To study antidepressant drug dispensation in the Spanish region of Andalusia and in the Almeria Health Area (AHA) over the past decade, analyzing the variability, trends, and influential factors. METHODS: We conducted an observational ecological study of antidepressant drug dispensation between 2000 and 2010 in Andalusia. Dispensation was measured as Defined Daily Dose (DDD) per 1,000 inhabitants per day. A multilevel analysis (STATA 11.1) was performed to determine the variability among the basic health zones (BHZs) (2004-2010) and influential factors. RESULTS: Between 2000 and 2010, the total dispensation of antidepressant drugs increased by more than 100 % in Andalusia and in the AHA. This increase was primarily caused by the greater dispensation of selective serotonin reuptake inhibitors (ATC-N06AB) and other antidepressants (ATC-N06AX). Multilevel analysis revealed a wide variability in the levels and trends of antidepressant dispensation among BHZs. Urbanicity and the percentage of immigrants in the BHZ were negatively associated with their dispensation, which was positively influenced by a higher proportion of women and over 65-year-olds in the population. CONCLUSIONS: The elevated dispensation of several groups of antidepressant drugs in this study population indicates the need for health policies to rationalize their use. Further research is required into the differences in antidepressant dispensations between immigrant and native populations and the implications for public health policies.

Pressure waves in the aorta during isolated abdominal belt loading: the magnitude, phasing, and attenuation.

While rupture of the aorta is a leading cause of sudden death following motor vehicle crashes, the specific mechanism that causes this injury is not currently well understood. Aortic ruptures occurring in the field are likely due to a complex combination of contributing factors such as acceleration, compression of the chest, and increased pressure within the aorta. The objective of the current study was to investigate one of these factors in more detail than has been done previously; specifically, to investigate the in situ intra-aortic pressure generated during isolated belt loading to the abdomen. Ten juvenile swine were subjected to dynamic belt loads applied to the abdomen. Intraaortic pressure was measured at multiple locations to assess the magnitude and propagation of the resulting blood pressure wave. The greatest average peak pressure (113.6 +/- 43.5 kPa) was measured in the abdominal aorta. Pressures measured in the thoracic aorta and aortic arch were 70 per cent and 50 per cent, respectively, that measured in the abdominal aorta. No macroscopic aortic trauma was observed. To the authors' knowledge the present study is the first one to document the presence, propagation, and attenuation of a transient pressure wave in the aorta generated by abdominal belt loading. The superiorly moving wave is sufficient to generate hydrostatic and intimal shear stress in the aorta, possibly contributing to the hypothesized mechanisms of traumatic aortic rupture.

Use of polyvinylidene fluoride (PVDF) meshes for ventral hernia repair in emergency surgery.

PURPOSE: The implantation of non-absorbable meshes is the gold standard technique for ventral hernia (VH) repairs. However, emergency surgeries are often related to contaminated/infected fields, where the implantation of prosthetic materials may not be recommendable. Our aim was to evaluate the results of polyvinylidene fluoride (PVDF) meshes used for contaminated and/or complicated VH repairs in the acute setting. METHODS: We conducted a retrospective analysis of patients with VH who underwent emergency surgery involving PVDF meshes, in a tertiary hospital (from November 2013 to September 2019). We analyzed postoperative complications and 1-year recurrence rates. We evaluated the relationships between contamination grade, mesh placement, infectious complications, and recurrences. RESULTS: We gathered data on 123 patients; their mean age was 62.3 years, their mean BMI was 31.1 kg/m2, and their mean CeDAR index was 51.6. 96.4% of patients had a grade 2-3 ventral hernia according to the Rosen index. The mean defect width was 8 cm (IQR 2-18). 93 cases (75.6%) were described as contaminated or dirty surgeries. A PVDF mesh was placed using an IPOM technique in 56.3% of cases, and via interposition location in 39.9%. The one-month recurrence rate was 5.7% and recurrence after one year was 19.1%. The overall mortality rate was 27.6%. Risk of recurrence was related to patients with a Rosen score over 2 (p < 0.001), as well as with postoperative SSI (p = 0.045). Higher recurrence rates were not related to PVDF mesh placement. CONCLUSION: The use of PVDF meshes for emergency VH repairs in contaminated surgeries seems safe and useful, with reasonable recurrence rates, and acceptable infectious complication rates, similar to those published in the literature.

Pharmacology and therapeutic potential of sigma(1) receptor ligands.

Sigma (sigma) receptors, initially described as a subtype of opioid receptors, are now considered unique receptors. Pharmacological studies have distinguished two types of sigma receptors, termed sigma(1) and sigma(2). Of these two subtypes, the sigma(1) receptor has been cloned in humans and rodents, and its amino acid sequence shows no homology with other mammalian proteins. Several psychoactive drugs show high to moderate affinity for sigma(1) receptors, including the antipsychotic haloperidol, the antidepressant drugs fluvoxamine and sertraline, and the psychostimulants cocaine and methamphetamine; in addition, the anticonvulsant drug phenytoin allosterically modulates sigma(1) receptors. Certain neurosteroids are known to interact with sigma(1) receptors, and have been proposed to be their endogenous ligands. These receptors are located in the plasma membrane and in subcellular membranes, particularly in the endoplasmic reticulum, where they play a modulatory role in intracellular Ca(2+) signaling. Sigma(1) receptors also play a modulatory role in the activity of some ion channels and in several neurotransmitter systems, mainly in glutamatergic neurotransmission. In accordance with their widespread modulatory role, sigma(1) receptor ligands have been proposed to be useful in several therapeutic fields such as amnesic and cognitive deficits, depression and anxiety, schizophrenia, analgesia, and against some effects of drugs of abuse (such as cocaine and methamphetamine). In this review we provide an overview of the present knowledge of sigma(1) receptors, focussing on sigma(1) ligand neuropharmacology and the role of sigma(1) receptors in behavioral animal studies, which have contributed greatly to the potential therapeutic applications of sigma(1) ligands.

[Drug-related mortality among inpatients admitted in Internal Medicine]. / Mortalidad hospitalaria asociada a medicamentos en un Servicio de Medicina Interna.

BACKGROUND: To analyze the mortality associated with prescriptions, the drugs most frequently involved and the associated risk factors in patients admitted to Internal Medicine. METHODS: A retrospective, observational study. The clinical records of adult patients who died consecutively in the department of Internal Medicine in a Spanish tertiary hospital over twenty-two months were reviewed. The main variable was the prevalence of hospital death suspected of being related to the medications administered during admission. RESULTS: Out of the 455 deaths analyzed, 22.2% were related to the medications received; in 55 cases (12.1%) the drugs were suspected of being the cause of death and in 46 cases (10.1%) of contributing to it. The most frequent diagnoses in cases of death associated with drugs were cardiac arrhythmia (23.7%), severe hemorrhage (19.8%) and aspiration pneumonia (12.8%). The drugs with the highest prevalence in deaths related to pharmacological treatment were an-tithrombotic drugs (23.7%), digoxin (21.7%), antipsychotics (17.8%) and benzodiazepines (14.8%). The only independent risk factor for mortality associated with treatment was the number of medications administered (OR=1.25, 95%CI: 1.14-1.37). No significant association was found with age, sex, number of pathologies or duration of hospital stay. CONCLUSION: A high percentage of deaths of patients admitted to Internal Medicine were considered related to the medications received. Antithrombotic drugs, digoxin and psychotropic drugs were the agents most frequently implicated. This mortality is independently and significantly associated with the number of medications administered.

Bacterial osteomyelitis: microbiological, clinical, therapeutic, and evolutive characteristics of 344 episodes.

OBJECTIVE: Osteomyelitis is a difficult-to-cure infection, with high relapse rate despite adequate therapy. Large published osteomyelitis series in adults are rare. METHODS: A total of 344 adult osteomyelitis patients were studied and followed > 12 months after hospital discharge. Demographic, microbiological, clinical, therapeutic and outcome data were analyzed. RESULTS: Mean age was 52.5 ± 18.3 years and 233 (67.7%) were male. Main osteomyelitis types were post-surgical (31.1%), post-traumatic (26.2%) and hematogenous (23%). Tibia (24.1%) and femur (21.8%), and methicillin-susceptible S. aureus (29.6%) were the most commonly involved bone and bacteria, respectively. Median follow-up was 12.0 (IQR 0-48) months. Inflammatory markers were increased in 73.6%. Overall, patients were treated by IV and oral routes with one (IV: 44.5%, oral: 26.7%), two (IV: 30.1%, oral: 21.8%) or ≥ 2 (IV: 15.2%, oral: 6.1%) antibiotics. Median duration on IV/oral antimicrobials was 28.0 (IQR 24-28) and 19.5 (IQR 4-56) days, respectively. Anti-staphylococcal ß-lactams cloxacillin/cefazolin (19.2%) and ciprofloxacin (5.5%) were the most frequently used IV and orally, respectively. Overall 234 (68.0%) underwent surgery, 113 (32.8%) debridement, 97 (27.4%) debridement + muscle flap and 24 (7%) amputation. At the end of follow-up 208 patients (60.6%) did not have relapsed. Operated patients had significantly less relapses (p<0.0001). A total of 23 (6.7%) died, 11 (3.2%) by infectious complications and 48 (14%) were lost in the follow-up. CONCLUSIONS: Osteomyelitis is due to different causes complicating its therapy. Risk factors or causal microorganism could influence its treatment and outcome. Aggressive surgery along with adequate antimicrobial therapy are mandatory for cure.

Inhibitory action of a met-enkephalin on ACTH release in man.

In order to study the mechanism of action of a Met-enkephalin (FK 33824) on the pituitary-adrenal axis eight normal male volunteers were subjected to an ACTH stimulation test. Lysine-vasopressing (LVP), 5 IU, was injected intramuscularly after pretreatment with 0.5 mg FK 33824 i.m. or a placebo. In six of the subjects the opiate was again administered preceding a single injection of 0.25 mg ACTH beta 1-24 i.m. Blood was collected at regular intervals and ACTH and cortisol concentrations analyzed in all samples. LVP induced significant plasma ACTH (P < 0.05) and cortisol (P < 0.001) increases. Pretreatment with FK 33824 completely antagonized the effect of LVP. Furthermore, the cortisol elevation after exogenous ACTH was not modified by previous administration of FK 33824. It is concluded that the Met-enkephalin derivative FK 33824 directly suppresses ACTH release from the pituitary without influencing adrenal synthesis of cortisol.

Recurrent Hepatocellular Carcinoma After Liver Transplantation: Analysis of Risk Factors.

BACKGROUND: Survival after orthotopic liver transplantation (LT) for hepatocellular carcinoma (HCC) is influenced by tumor recurrence. This study examines the survival of patients who underwent LT for HCC and developed recurrence of tumor after transplantation. METHODS: A retrospective analysis was performed of the 200 patients who underwent LT secondary to HCC from 1990 to 2014. We excluded 19 patients from the study owing to early postoperative deaths in the 1st month. We divided our sample into 2 groups according to the presence of recurrence. We performed a univariate analysis to identify variables that are significantly associated with the risk of recurrence. Afterward we use multivariate analysis regression analysis to find independent significance. RESULTS: Univariate analysis shows significant relationship between high Edmondson-Steiner grades (G3-G4) and the development of tumor recurrence. Tumor size, vascular invasion, and capsular invasion were found to be independent risk factors of tumor recurrence in the multivariate analysis. CONCLUSIONS: Tumor recurrence defines survival of patients who underwent LT for HCC. In this study we discuss which histologic factor are associated with higher risk of tumor recurrence, and therefore a negative the impact on patient's survival.

Cribiform variant of papillary thyroid cancer and familial adenomatous polyposis.

BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome characterised by the progressive development of multiple colorectal adenomatous polyps and an increased incidence of colorectal carcinoma. It is often accompanied by other benign or malignant extracolonic manifestations, including gastric and duodenal tumours, osteomas, desmoid tumours, retinal pigmentation, and thyroid and adrenocortical tumours METHODS AND RESULTS: We report the case of a 42-year-old white female with FAP who was referred to our Endocrine Surgery Unit for surgery because of a palpable mass in the left side of the neck. An ultrasound-guided fine needle aspiration biopsy showed a cribriform-morular variant (CMV) of papillary thyroid carcinoma (PTC). The incidence, clinical presentation, histology and treatment options for this rare histological subtype are discussed. CONCLUSIONS: The diagnosis of CMV of PTC is very strongly related to the FAP syndrome and must be suspected when a thyroid node appears in FAP patients. Likewise, any patient without known FAP who presents this histology in a surgically biopsied or resected thyroid node should undergo total colonoscopy for screening of colonic polyposis and genetic study of the APC gene sequence.

Inhibitory effect of bromocriptine treatment on luteinizing hormone secretion in polycystic ovary syndrome.

In order to investigate a possible common role of central dopaminergic mechanisms in the release of PRL and LH in patients with the polycystic ovary syndrome (PCO), plasma LH pulsatile profiles and the response to GnRH were studied in a group of 12 PCO patients before and after 3 months of treatment with bromocriptine, 2.5 mg twice daily. They were divided into two groups of six patients according to the occurrence or not of hyperprolactinemia (plasma PRL, 30.3 +/- 2.7 (SE) ng/ml vs. 9.5 +/- 0.8 (SE) ng/ml). Integrated LH secretion significantly decreased in hyperprolactinemic [2537 +/- 371 (SE) vs. 907 +/- 102 mIU/ml X min] as well as in normoprolactinemic (2847 +/- 460 vs. 901 +/- 152 mIU/ml X min) patients, but there was no difference in the response of the two groups. The LH increment after a bolus injection of 100 micrograms GnRH was reduced (P less than 0.01) to the same extent in both groups. These results indicate a dopaminergic component in the control of LH release in PCO patients, independent of the mechanism governing PRL secretion. Since bromocriptine reduced LH secretion, it may be useful for the management of this condition.

Inhibitory effect of guanfacine, a central alpha-adrenoceptor agonist, on prolactin secretion stimulated by insulin-induced hypoglycemia.

In six normal male volunteers oral administration of an alpha-receptor agonist, guanfacine (1 mg/q.i.d. for 4 days), had no effect on PRL release induced by 5 mg metoclopramide iv. The same treatment with quanfacine in six other normal subjects significantly reduced PRL secretion stimulated by insulin-induced hypoglycemia (P less than 0.05). These results suggest that an adrenergic pathway, hypothalamic or extrahypothalamic, might be involved in the inhibitory control of PRL secretion.

Induced human gestational hypoprolactinemia: lack of action on fetal adrenal androgen synthesis.

To investigate the possible role of PRL in the control of fetal adrenal function, blood samples were collected from maternal peripheral and cord blood from six women at delivery, who had received treatment with bromocriptine (3.75--35 mg daily) for the entire gestation. A group of eight untreated parturients served as control. Parameters measured were PRL and dehydroepiandrosterone, the latter as an indicator of fetal adrenal function. PRL was significantly suppressed (P < 0.002), whereas dehydroepiandrosterone was not influenced by bromocriptine treatment. The results indicate that the control of fetal production of androgenic substrate by the adrenals is not specifically PRL dependent.

SMS 201-995 induces a continuous decline in circulating growth hormone and somatomedin-C levels during therapy of acromegalic patients for over two years.

Ten acromegalic patients, four previously untreated, were studied before and at regular intervals during treatment with the long-acting somatostatin analog SMS 201-995 (200-300 micrograms daily for 2 or 3 sc injections for 16-108 weeks). All patients had rapid clinical improvement, with disappearance of excessive perspiration, paresthesias, and headache within the first 6 weeks of therapy. The mean 24-h serum GH concentrations fell from 44.0 +/- 7.8 (+/-SE) micrograms/L before to 5.9 +/- 1.0 microgram/L at the end of therapy. The GH levels from 2-6 h after the acute administration of 50 micrograms SMS 201-995 before the start of therapy correlated significantly with the mean 24-h GH concentrations after 16-108 weeks of treatment (P less than 0.05). The initially increased serum somatomedin-C (Sm-C) levels normalized in 5 of these 10 patients; the mean values were 7.3 +/- 0.9 U/mL before and 2.9 +/- 0.7 U/mL at the end of therapy. The Sm-C and mean GH levels continuously decreased during long term therapy; the concentrations after 1.5-2 yr of therapy were significantly lower than those after 6-12 months of therapy (P less than 0.01 and P less than 0.01, respectively). A slight decrease in the size of the pituitary tumor was noted by computed tomography in three of six patients. Transient clinically detectable steatorrhea occurred in two patients. Postprandial hyperglycemia occurred during therapy in eight patients, while in two patients with type 2 diabetes mellitus carbohydrate tolerance improved in one and deteriorated in the other. SMS 201-995 is a highly effective medical treatment for acromegaly. Clinically improvement occurs rapidly, and the inhibition of serum GH and Sm-C levels persisted even after more than 1 yr of therapy. No important subjective side-effects were noted. SMS 201-995 is an excellent drug in patients in whom acromegaly persists after surgery and for interim treatment to shorten the period of clinical activity after irradiation.

A comparison among the growth hormone-lowering effects in acromegaly of the somatostatin analog SMS 201-995, bromocriptine, and the combination of both drugs.

The acute GH inhibitory effects of 50 micrograms SMS 201-995, a somatostatin analog, and 2.5 mg bromocriptine were compared in 17 acromegalic patients. SMS 201-995 suppressed plasma GH levels after 2-6 h to 5 micrograms/liter or less in 10 of these 17 patients, while bromocriptine did the same in only 5 of them. There was much variation in the responsiveness to both drugs in these patients, but the GH-lowering effect of 50 micrograms SMS 201-995 was significantly greater than that of 2.5 mg bromocriptine. SMS 201-995 and bromocriptine together significantly suppressed plasma GH levels in 2 of 3 acromegalic patients who were insensitive to both compounds when tested separately. We conclude that most acromegalic patients respond better to SMS 201-995, while a few patients are more sensitive to the GH-lowering effect of bromocriptine. In addition, the combination of SMS 201-995 and bromocriptine can be of value in a few acromegalic patients who do not respond to either drug alone.

The somatostatin analog SMS 201-995 induces long-acting inhibition of growth hormone secretion without rebound hypersecretion in acromegalic patients.

The acute effect of the somatostatin analog SMS 201-995 (SMS) was investigated in eight acromegalic patients. This substance is an octapeptide [DPhe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-(ol)] that inhibits GH release in experimental animals and man. After a control day, 50 micrograms SMS were injected sc, and plasma GH and insulin and blood glucose levels were measured at multiple intervals for 24 h. GH significantly (P less than 0.001) decreased in seven of eight acromegalic patients from 30 +/- 5 (+/- SE) to an average of 10.7 +/- 4 micrograms/l from 1-10 h after drug administration. No rebound effect occurred. Postprandial blood glucose levels were significantly (P less than 0.01) higher between 2 and 4 h after SMS treatment compared with control day values, and there was a substantial reduction in insulin secretion, as estimated by the area under the curve (P less than 0.01), during the first 3 h after SMS administration. Circulating GH was not altered by SMS or the dopamine agonist mesulergine in one patient, but the combination of both substances (50 micrograms SMS, sc, and 0.5 mg mesulergine, orally) reduced GH to below 50% of basal. In vitro studies showed that 1 PM, 0.1 nM, and 10 nM SMS or natural somatostatin exerted a similar inhibitory effect (12-39% reduction; P less than 0.01 for all three strengths) on GH release by cultured human pituitary tumor cells. In conclusion, the somatostatin derivative SMS exerts a potent and prolonged inhibitory action on GH secretion and a shorter lasting suppression of insulin in acromegalic patients. Therefore, it may represent a useful tool in the chronic management of this condition.

Failure of maintained hyperprolactinemia to improve lactational performance in late puerperium.

Although stimulation of PRL secretion in the early postpartum period has been found to improve lactational performance, the effect of chronic maintenance of elevated plasma PRL levels on milk production is not known. In a randomized design, 66 lactating women were assigned to receive either a placebo (n = 32) or the dopamine antagonist sulpiride (n = 34; 100 mg, three times daily), for 4 days, followed by 50 mg, three times daily, for a 90-day period). Their basal and 30 min postsuckling plasma PRL levels as well as the weights of their infants were measured 1, 4, 15, 30, 60, and 90 days postpartum. Forty-one women (20 sulpiride-treated and 21 placebo-treated) completed the study. Compared with the placebo group, which had the expected postpartum plasma PRL decline, the sulpiride-treated women maintained significantly elevated basal plasma PRL values up to the 90th postpartum day. In contrast, the postsuckling plasma PRL level was significantly diminished in the latter group, and on day 90 was practically absent. On day 15, weight gain was significantly greater in the infants whose mothers received sulpiride, but later, no differences were detectable between groups of infants despite the disparity in PRL levels in their mothers. We conclude that enhancement of PRL secretion in the early postpartum period may transiently increase milk production, but chronic hyperprolactinemia has no effect on lactational performance. The plasma PRL response to suckling is not essential for the maintenance of milk secretion. Instead, basal plasma PRL levels and neurogenic reflexes may be more instrumental in maintaining established lactation.