L-arginine promotes gut hormone release and reduces food intake in rodents.

AIMS: To investigate the anorectic effect of L-arginine (L-Arg) in rodents. METHODS: We investigated the effects of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G-protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. RESULTS: Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L-Arg suppressed food intake in rats. CONCLUSIONS: L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity.

Neonatal lipopolysaccharide exposure delays puberty and alters hypothalamic Kiss1 and Kiss1r mRNA expression in the female rat.

Immunological challenge experienced in early life can have long-term programming effects on the hypothalamic-pituitary-adrenal axis that permanently influence the stress response. Similarly, neonatal exposure to immunological stress enhances stress-induced suppression of the hypothalamic-pituitary gonadal (HPG) axis in adulthood, but may also affect earlier development, including the timing of puberty. To investigate the timing of the critical window for this programming of the HPG axis, neonatal female rats were injected with lipopolysaccharide (LPS; 50 microg/kg i.p.) or saline on postnatal days 3 + 5, 7 + 9, or 14 + 16 and monitored for vaginal opening and first vaginal oestrus as markers of puberty. We also investigated the effects of neonatal programming on the development of the expression patterns of kisspeptin (Kiss1) and its receptor (Kiss1r) in hypothalamic sites known to contain kisspeptin-expressing neuronal populations critical to reproductive function: the medial preoptic area (mPOA) and the arcuate nucleus in neonatally-stressed animals. We determined that the critical period for a significant delay in puberty as a result of neonatal LPS exposure is before 7 days of age in the female rat, and demonstrated that Kiss1, but not Kiss1r mRNA, expression in the mPOA is down-regulated in pre-pubertal females. These data suggest that the mPOA population of kisspeptin neurones play a pivotal role in controlling the onset of puberty, and that their function can be affected by neonatal stress.

Probability of finding T1a and T1b (incidental) prostate cancer during TURP has decreased in the PSA era.

The purpose of this study is to assess the likelihood of detecting stage T1a and T1b cancer in transurethral prostatectomy specimens during the PSA era. Comparison was made of transurethral resection of prostate (TURP) cohorts in the pre-PSA era (1986-1987) and the PSA era (1994-2000), excluding patients with known PCa. A total of 228 men without a known history of prostate cancer underwent TURP during the pre-PSA era time frame and 501 underwent the procedure during the PSA era time frame. Malignancy diagnosed at the time of TURP decreased from 14.9 to 5.2% of patients in the pre-PSA and PSA eras, respectively. Stage T1a decreased from 4.4 to 2.4% and Stage T1b decreased from 10.5 to 2.8% of patients in the pre-PSA and PSA eras, respectively (P<0.001, Fisher's exact test). Prostate cancer newly identified during TURP has decreased significantly in the era of PSA screening in our study population, with the most significant drop being in clinically significant stage T1b. The decrease in TURP rates reduces the overall incidence of T1a/b cancer but cannot explain the lower risk of detecting previously unsuspected cancer at the time of any given TURP. Identification of many men with occult prostate cancer before TURP through screening and early detection is the most likely cause of this finding. These data suggest that men considering surgical or medical management of benign prostatic hyperplasia may be informed that it should be infrequent that men properly evaluated for prostate cancer will harbor clinically significant undetected malignancy.

Down-regulation of hypothalamic kisspeptin and its receptor, Kiss1r, mRNA expression is associated with stress-induced suppression of luteinising hormone secretion in the female rat.

Identification of kisspeptin (Kiss1) and its G protein-coupled receptor 54 (Kiss1r) as an essential component of the hypothalamic-pituitary-gonadal (HPG) axis controlling gonadotrophin secretion raises the possibility that kisspeptin-Kiss1r signalling may play a critical role in the transduction of stress-induced suppression of reproduction. We examined the effects of: (i) three different stressors, known to suppress pulsatile luteinising hormone (LH) secretion; (ii) corticotrophin-releasing factor (CRF); and (iii) corticosterone on Kiss1 and Kiss1r expression in key hypothalamic sites regulating gonadotrophin secretion: the medial preoptic area (mPOA) and arcuate nucleus (ARC). Ovariectomised oestrogen-replaced rats were implanted with i.v., subcutaneous or i.c.v. cannulae. Blood samples were collected at 5-min intervals for 5-6 h for detection of LH. Quantitative reverse transcriptase-polymerase chain reaction was used to determine Kiss1 and Kiss1r mRNA levels in brain punches of the mPOA and ARC collected 6 h after restraint, insulin-induced hypoglycaemia or lipopolysaccharide stress, or after i.c.v. administration of CRF, or acute or chronic subcutaneous administration of corticosterone. We observed down-regulation of at least one component of the kisspeptin-Kiss1r signalling system by each of the stress paradigms within the mPOA and ARC. CRF decreased Kiss1 and Kiss1r expression in both the mPOA and ARC. Both acute and chronic stress levels of corticosterone resulted in a concomitant decrease in Kiss1 and an increase in kiss1r mRNA expression in the mPOA and ARC. This differential regulation of Kiss1 and Kiss1r might account for the lack of effect corticosterone has on pulsatile LH secretion. Considering the pivotal role for kisspeptin-Kiss1r signalling in the control of the HPG axis, these results suggest that the reduced Kiss1-Kiss1r expression may be a contributing factor in stress-related suppression of LH secretion.

Periprostatic local anesthesia eliminates pain of office-based transrectal prostate biopsy.

Up to 96% of patient who undergo prostate biopsy report pain. We performed periprostatic local anesthesia injection in an effort to improve patient acceptance of prostate biopsy. Sixty patients were randomized to receive either local injection of lidocaine in the periprostatic nerves or no anesthetic. Lidocaine was injected through a 7-inch spinal needle placed through a transrectal ultrasound biopsy guide. Ten-core biopsies were immediately performed. Following biopsy, all patients gave a Visual Analog Scale (VAS) assessment of their pain experienced during biopsy.A majority of patients reported Visual Analog Scale (VAS) scores in the moderate (28.6%) or severe (28.6%) ranges unless local anesthesia was given. Only one of 27 patients (3.7%) receiving local anesthetic reported moderate pain, and none reported severe pain. Mean VAS pain scores were 1.4 in the anesthetic group and 4.5 in the control group (P<0.0001). No difficulty was encountered from scarring in the five patients who underwent nerve spring radical retropubic prostatectomy following local anesthetic injection. Periprostatic injection of local anesthetic essentially eliminates pain from prostate biopsy. Nerve-sparing radical retropubic prostatectomy is not more difficult as a result.

Effect of temperature and pH adjustment of bupivacaine for intradermal anesthesia.

To determine the effects of warming and buffering of 0.5% bupivacaine on the pain associated with intradermal injection and the time of onset of anesthesia, 40 adult volunteers were entered into a randomized, double-blind study conducted at a community teaching hospital. The three-part study compared room temperature (20 degrees) bupivacaine buffered to a pH of 7.1 with the following solutions: buffered bupivacaine warmed to 37 degrees C, unbuffered bupivacaine at room temperature, and unbuffered bupivacaine warmed to 37 degrees C. The same crossover protocol was followed for each part of the study. Subjects received 0.5-mL intradermal injections through 27-gauge needles over 30 seconds, one study solution in each forearm. Immediately after each injection, pain was assessed using a 100-mm visual analog pain scale. The time of onset of anesthesia (loss of intradermal sensation to pinprick) was measured by stopwatch. The mean perceived pain score for the warm buffered bupivacaine (51 mm) was significantly lower than for the room temperature buffered solution (63 mm, P = .003). Similarly, there was a statistical difference between the room temperature buffered and unbuffered solutions (65 v 78 mm, P < .001). The differences in mean pain scores for the room temperature buffered bupivacaine, compared with the other three solutions, suggest that warming and buffering have an additive effect. In this model, the latency of action of bupivacaine was not affected by alkalinization. However, warming bupivacaine to 37 degrees C reduced the time of onset to intradermal anesthesia by 12.1 seconds (95% confidence interval, 0.6 to 23.6). These results suggest that warming is more effective than buffering to reduce the pain of infiltration of bupivacaine and the time of onset of intradermal anesthesia.

A survey of the availability of dental services to developmentally disabled persons residing in the community.

Public Law 88-164, enacted in 1963, has led to extensive deinstitutionalization of persons with mental retardation from a peak census of 194,650 in 1967 to 91,440 by 1988. This population now depends on the community-based health care system for medical and dental care. A survey conducted to determine the availability of dental care to the developmentally disabled residing in group homes located in north central Florida indicated that 40% of caretakers experienced difficulty in locating dentists willing to provide comprehensive dental services for residents. According to the caretakers, although 75% of the residents were cooperative dental patients, dentists were reluctant to provide services for a variety of reasons, including financial disincentives, inadequate knowledge and preparation, and a lack of proper equipment necessary to treat this group of special patients.

Institutional structures: catalysts of or barriers to quality care for the institutionalized aged in Scotland and the U.S.

The care of the elderly in two long-term care institutions, one in Scotland and one in the United States, is described, compared, and analyzed. In Scotland three institutional structures, the National Health Service, the Geriatric Service, and the specialty of geriatrics are identified as catalysts of quality care. In the U.S. Medicare and Medicaid, the absence of geriatrics as a specialty, and the nursing home are identified as barriers to quality care for the institutionalized aged. The findings suggest that three components, an adequate government insurance program, professionals who specialize in the care of the aged, and a structure to provide continuing comprehensive care, are essential for a successful program of care for the institutionalized elderly.