A pharmacokinetic study of injectable testosterone undecanoate in hypogonadal men

OBJECTIVE: In rodents, leptin is involved in regulating eating behaviour, fat storage, and reproductive function. In humans, the serum leptin concentration in obese and normal weight subjects correlates with body mass index, reflecting the body fat store. The serum leptin exhibit diurnal variation, however, this has been reported to be absent in normal weighted amenorrheic athletes. Anorexia nervosa is associated with multiple endocrine abnormalities. Hypothalamic amenorrhoea often precedes the weight loss and may persist after weight recovery. We hypothesized that leptin could be involved in the regulation of eating behaviour and gonadal function in anorexia nervosa. DESIGN: We measured the concentration of leptin in serum samples taken after an overnight fast in 18 female anorexia nervosa patients and 11 controls. To study diurnal variation, eight patients and 11 controls were hospitalized for 24 h and had a standardized diet at regular times. Seven blood samples were obtained at 4 h intervals from each subject. PATIENTS: The patients fulfilled the DSM-IV criteria for anorexia nervosa. The mean body mass index for the patients was 14.2 +/- 2.3 kg/m2 and for controls 20.3 +/- 1.7 kg/m2. RESULTS: The mean fasting leptin concentration as well as the 24 h mean concentration were significantly lower in the anorectic group than in the control group (2.5 +/- 0.9 vs 10.1 +/- 6.1 micrograms/l, P < 0.01 and 2.7 +/- 1.5 vs 10.6 +/- 7.1 micrograms/l, P < 0.01 respectively). In the whole group of subjects (n = 28) a significant positive correlation between the leptin level and body mass index was found (r = 0.63, P < 0.001). In the anorectic group it was found that the leptin level correlated better with body fat percentage than with body mass index. In normalized data the time course of the mean leptin levels showed a monophasic variation with nadir and zenith at about 0900 and 0100 h respectively. However, the individual coefficients of variance were significantly lower in the anorectic group compared to the group of healthy women. CONCLUSION: In patients with anorexia nervosa the leptin level is low, reflecting the low body fat mass, and the relative diurnal variation is strikingly reduced. The similarity to that of normal weighted women with hypothalamic amenorrhoea suggest that altered leptin oscillations may be of particular significance in the hypothalamic regulation of reproductive function.     

Lymphatic absorption and metabolism of orally administered testosterone undecanoate in man

[3H]-testosterone undecanoate ([3H]TU) was administered orally to 4 patients with a thoracic duct catheter after neck dissection surgery. Appearance of radioactivity in lymph, plasma and urine was measured at different times. Metabolites of TU in these fluids were investigated. Peak levels of radioactivity appeared simultaneously in lymph and plasma (2.5-5 h after administration) while the excretion in urine was highest approximately 2 h after the plasma and lymph peak. The main compounds appearing in the lymph were TU and 5alpha-dihydrotestosterone undecanoate (5alpha-DHTU), but 5beta-DHTU could not be detected. In plasma almost all metabolites were probably conjugated. During the first 24 h approximately 40% of the administered radioactivity was excreted in the urine. The total amount of radioactivity excreted in the urine during the first week was 45-48%. The predominant urinary metabolites were testosterone- and androsterone-glucuronide. The results indicate that TU is metabolized partly in the intestinal wall. The remaining TU and newly-formed 5alpha-DHTU, at least partly, are absorbed via the lymphatic system.     

The role of outfracture in correcting post-rhinoplasty nasal obstruction

Post-rhinoplasty nasal osbtruction is often related to narrowing in the region of the nasal valve. Correction of this obstruction can include inferior turbinectomy, septoplasty spreader grafts and nasal valvuloplasty. The authors have seen cases of severe valve stenosis related to infracture after osteotomy which did not respond to any of the aforementioned procedures. These patients were treated with revision osteotomy with outfracture. We discuss patient selection and surgical technique for revision osteotomy with outfracture as well as a cadaver dissection demonstrating the effects of infracture and outfracture on valve area. The clinical results, based on patient satisfaction and pre- and postoperative photographs, are presented. Revision osteotomy with outfracture should be included in the surgeon's armamentarium for the treatment of post-rhinoplasty nasal obstruction.     

The combination of testosterone undecanoate with tamoxifen citrate enhances the effects of each agent given independently on seminal parameters in men with idiopathic oligozoospermia

OBJECTIVE: To evaluate the effects of combined tamoxifen citrate and T undecanoate treatment on seminal parameters in men with idiopathic oligozoospermia. DESIGN: Prospective randomized clinical study. SETTING: A state hospital tertiary clinic. PATIENT(S): Eighty oligozoospermic men were included in the protocol. INTERVENTION(S): Patients were randomized to receive placebo, T undecanoate (40 mg three times per day), tamoxifen citrate (10 mg two times per day), or T undecanoate plus tamoxifen citrate. RESULT(S): Tamoxifen citrate plus T undecanoate treatment produced a satisfactory improvement of total sperm number, motility, and functional sperm fraction after 3 and 6 months. Comparisons with other active treatment groups showed significantly higher increment values for motility and functional fraction, whereas aniline, acrosine, and free L-carnitine also were markedly better in the combination treatment group. CONCLUSION(S): These results indicate that the combination of tamoxifen citrate with T undecanoate not only improves significantly important seminal parameters but also compares favorably with the single treatments used. Therefore, this combination deserves a place as a first line of treatment in idiopathic oligozoospermia.     

The role of bruxism in the appearance of temporomandibular joint disorders

Bruxism is a parafunction observed both in young and adult populations. The mean prevalence is about 20% and is decreasing with age. Women appear to clench more frequently than men. Often, bruxism is understood as both clenching with occasional tooth contact or grinding. A correct and validated definition has only recently been suggested. Many symptoms are assigned to this process, although few symptoms scientifically can be used as specific diagnostic criteria. The symptoms most often associated with bruxism like muscle-stiffness and -pain, limitation of mouth opening. TMJ-internal derangements, toothwear, are also found in TMD-patients. Because the bruxism-process is not only a problem for the patient, who suffers from pain, dysfunction and possible toothwear, it concerns also the dentist. It is essential that those who treat the bruxist-patient, have an understanding of the etiology, diagnosis and management of bruxism, of the many described oral parafunctional behaviors (oromotor behavior). This literature-review could not find a causal etiological mechanism between the occurrence of TMD-symptoms and the bruxism although a relationship between those two conditions has been described.     

A protective role for testosterone in adjuvant-induced arthritis

We have investigated the role of the gonadal steroids testosterone (T) and progesterone in modulating: (1) the onset and severity of adjuvant-induced arthritis (AA), (2) the response of the hypothalamo-pituitary-adrenal (HPA) axis, and (3) the levels of plasma prolactin and anterior pituitary prolactin messenger ribonucleic acid (mRNA) in the rat. Male rats were castrated (CSX) and received either no T, low T or high T delivered using silastic implants. In a second study experimental groups comprised CSX/AA, CSX/AA + progesterone or CSX/AA + progesterone + T. The time of onset was sooner and the severity of AA was greater in CSX rats. Inflammation was prevented by T replacement. Endogenous plasma T levels were decreased in AA rats. In control animals with AA there was an increase in pro-opiomelanocortin (POMC) mRNA in the anterior pituitary and of plasma corticosterone, and a decrease in corticotrophin-releasing factor (CRF) mRNA. These changes in the HPA axis of AA and CSX/AA rats were reversed by T replacement. These data suggest that T has an important protective effect on the progress and severity of AA. This was reflected by a reversal of the neuroendocrine changes of the HPA axis. Progesterone treatment alone had no effect on the severity of the disease. Prolactin mRNA in the anterior pituitary was decreased in the CSX and in the CSX/AA group but was not altered by AA. Plasma prolactin was raised in AA but T replacement did not reduce these elevated levels despite the absence of disease. Thus, prolactin provides a poor indicator of inflammation, suggesting that it may not be a potent pro-inflammatory compound in AA.     

The role of function in conceptual development.

40 3-, 40 5-, and 40 7-yr-olds were administered a free-sorting task, a directed sorting task, a verbal labeling task, and a conversation task using 4 natural concepts: cup, scissors, money, and musical instrument. Results reveal that almost all Ss had a knowledge of the correct function for cup and scissors, and all but the 3-yr-olds knew similar information for money and musical instrument. However, none of the Ss used all of the knowledge they possessed to guide behavior in the free-sorting task. The 5- and 7-yr-olds could use their knowledge when cued in the directed sort and when forced to use it in the verbal labeling task. In comparison, the 3-yr-olds were relatively unable to use their knowledge to guide behavior in any of these 3 tasks. Inferences are drawn about both the structure of children's concepts and how that structure changes with development. (French abstract) (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of the lateral pterygoid muscles in TMJ disorders during static conditions

Intramuscular EMG of the lateral pterygoid muscles (LPM), surface EMG of the temporalis and masseter muscles and force measurements of the temporomandibular joint (TMJ) were synchronously used to investigate the biomechanical role of the two heads of the LPM in relation to internal derangement (ID) of the TMJ. EMG and kinetic analysis of five static conditions (resting, protraction, opening, molar and incisor clenching) and three maximum isometric masticatory forces (opening, molar and incisor clenching) were done to compare forces and muscular activity between TMJ ID and control subjects. The analysis of variance results of the integrated linear envelope (LE) EMG showed no significant differences between the two groups for the masseter and temporalis muscles. Therefore, there is no apparent reason to believe that these muscles are hyperactive in TMJ ID. The integrated LE EMG of the SLP was significantly lower in the TMJ group during molar clenching (104 microV + 60.0 over 159 microV + 68.8 for a p = .020). The superior head of the lateral pterygoid muscle (SLP) seemed to have lost its diskal stabilizing function. The integrated LE EMG signals of the ILP were significantly higher in the TMJ ID group during rest, resisted protraction and incisor clenching (p = .029, p = .046, p = .031 respectively). The ILP muscle has probably adapted to control the inner joint instability while continuing its own actions. The ILP muscle seemed to have lost its functional specificity. The results of the isometric forces showed that TMJ ID subjects exhibited significantly lower molar bite forces (297.1N over 419N, p = .042) confirming that they have less muscle strength and tissue tolerance than subjects with healthy masticatory muscle systems. A neuromuscular adaptation could be occurring in the TMJ ID masticatory system affecting muscular actions and forces.     

The role of values in the nature/nurture debate about psychiatric disorders

This paper discusses the role that values play in our estimates of the relative importance of nature/nurture factors in the etiology of psychiatric disorders. It is argued that all parameter estimates, heritability estimates, variance explained, odds ratios, and relative risks, are based, at least in part, on value judgements that are made in the course of our research activities. Four aspects of causal inference where values are particularly influential are discussed: gene/environment interactions, environmental specificity, the distinction between causes of variation and the causes of a factor, and the reification of our measures. The value component in our research is illustrated in two areas of research: life events and depression and individual factors in violence.     

Defecation disorders and the role of defecography

This continuing education article discusses abnormalities of defecation and the physical mechanisms by which these abnormalities occur. The article also describes the role of defecography and other imaging techniques used to diagnose abnormalities of defecation.     

The role of the forestomachs in the adaptation of the alimentary function in ruminants

Dietary character of ruminants in the north is principally different between "nonselective" (cattle, sheep) and "selective" (reindeer, moose) species. Due to the developed polyfunctioning, forestomach in ruminants, primarily rumen and reticulum, are involved in the homeostasis formation in enteral and interior mediums, nutrients deposition and recirculation. That provides efficiency in utilization of deficient in nutrients forage and body reserves of wild ruminants during the winter. The original functional organization of absorption processes and nutrients recirculation across the multilayer epithelium of forestomach also promotes realization of the two levels metabolism during the year and adaptation of wild ruminants to season dynamics of nutrition.     

Leukocyte function in chronic myeloproliferative disorders

The myeloproliferative disorders (MPD) are clonal diseases that originate from a transformed stem cell and involve all myeloid lineage. The affected cells have both proliferative and functional impairment. Therefore, we evaluated and compared neutrophil function in 31 patients with polycythemia vera (PV), idiopathic myelofibrosis (MF), chronic myeloid leukemia (CML), and essential thrombocytosis (ET). Neutrophil chemotaxis, random migration, bactericidal activity and superoxide anion release in these patients were simultaneously compared to those of 31 healthy controls. In this study, chemotactic activity was significantly impaired in patients with PV and CML as compared to controls (M+/-SE: 42 +/- 6 vs. 69+/- 5 cells/field; p<0.005 and 47+/-7 vs. 68+/- 5; p<0.05, respectively). The assessment of the bactericidal activity of neutrophils showed no impairment in most of the patients. In the CML group, the serum had a very strong "lytic" effect on bacteria, possibly due to the high levels of serum lysozyme (22 +/- 2 microgram/ml). The superoxide anion release was found to be normal in most of the patients. Nevertheless, in 25% of PV patients the superoxide production was impaired (less than 60% of the simultaneous controls). In ET most patients had normal neutrophil function. Regarding the effect of treatment, neutrophil chemotactic activity was found to be significantly reduced in the hydrea-treated patients, as compared to the non- treated patients (p<0.001) or healthy controls (<0.0001). We conclude that disturbances in neutrophil function are present in patients with various MPDs, except ET. This probably reflects abnormal maturation of ancessors of the damaged stem cells. Nevertheless, we should keep in mind that therapy itself could affect neutrophil functions. This matter should be studied more extensively. Although infections are not common in MPD disorders, they occasionally occur. It is possible that impairment in the phagocytic function contribute to the development of infections in patients with myeloproliferative disorders.     

Electroencephalographic findings in liver function disorders

Abnormal rhythmisations in the EEG are described in hepatoportal encephalopathy as an expression of a disturbance of more profound cerebral structures. The EEG gives an actual information about the state of the cerebral functions of all stages of a hepato-cerebral decompensation and allows a reliable prognostic estimation during the observation of the course. Practically significant are also bioelectric findings of a disturbance of the cerebral function with clinically symptom-poor course in compensated liver cirrhosis or obstructive icterus.     

The role of pharmacy in the management of patients with temporomandibular disorders and orofacial pain

OBJECTIVE: To provide information regarding the current understanding of the etiology and treatment, both nonpharmacologic and pharmacologic, of orofacial pain conditions including temporomandibular disorders (TMDs). This review briefly discusses the etiology and pathophysiology underlying the development of TMDs, generally accepted nonpharmacologic methods of treatment, and the most common current pharmacologic management approaches. DATA SOURCES: Current medical literature and the authors' clinical experiences. DATA SYNTHESIS: TMDs encompass a number of diagnostic subgroups that involve the masticatory musculature, the temporomandibular joint(s), and associated structures. More than 10 million individuals in the United States are affected by TMDs. Most current pharmacologic management approaches in the treatment of orofacial pain conditions, including TMDs, involve the use of antidepressants, anticonvulsants, muscle relaxants, corticosteroids, and nonsteroidal anti-inflammatory drugs. CONCLUSION: Inclusion of pharmacists who are knowledgeable in the nonpharmacologic and pharmacologic treatment approaches on the TMD management team would improve therapeutic monitoring, follow-up, and outcomes in these patients.