Blood pressure development of the spontaneously hypertensive rat after concurrent manipulations of dietary Ca2+ and Na+. Relation to intestinal Ca2+ fluxes.

The blood pressure of the spontaneously hypertensive rat (SHR) is influenced by the Ca2+ content of its diet. As the SHR's greater dependence on dietary calcium may reflect a defect in intestinal calcium absorption, we measured in vitro unidirectional Ca2+ flux (J) in the duodenum-jejunum (four segments each) of the SHR (n = 6) and the normotensive Wistar-Kyoto rat (WKY; n = 6) by a modified Ussing apparatus. Because of the known and postulated interactions between Ca2+ and Na+ in both intestinal and vascular tissue, we assessed in vivo the influence of a concurrent manipulation of Na+ intake (three levels: 0.25%, 0.45%, and 1.0%) on the blood pressure development of SHRs (n = 35) and WKYs (n = 35), between 6 and 20 wk of age, exposed to three levels of dietary calcium (0.1, 1.0, and 2%). Net calcium flux (Jnet) (mean +/- SEM) was significantly (P less than 0.01) lower in the SHR (-2.8 +/- 6.3 nmol/cm2 X h) than in the WKY (34.6 +/- 8.8 nmol/cm2 X h). The SHR's decreased Jnet resulted from a significantly (P less than 0.03) lower mucosa-to-serosa flux (Jm-s) in the SHR (41.0 +/- 5.6 nmol/cm2 X h) compared with the Jm-s of the WKY (70.1 +/- 9.1 nmol/cm2 X h). Serosa-to-mucosa flux for calcium did not differ between the SHR (43.8 +/- 6.6 nmol/cm2 X h) and the WKY (35.5 +/- 8.0 nmol/cm2 X h). The SHR's decreased (P less than 0.002) Jm-s was confirmed by additional measurements in SHRs and WKYs. Jm-s was 36.2 +/- 3.7 nmol/cm2 X h in the SHRs (n = 11) and 64.4 +/- 6.7 nmol/cm2 X h in the WKYs (n = 9). The provision of an increased dietary Ca2+ (2% by weight) and increased Na+ (1%) to the SHR prevented the emergence of hypertension (P less than 0.001) (mean +/- SEM systolic blood pressure at 20 wk of age; 135 +/- 5 mmHg for the 2% Ca2+, 1% Na+ SHR vs. 164 +/- 2 mmHg for the control diet SHR). Ca2+ (0.1%) and Na+ (0.25%) restriction accelerated the SHR's hypertension (192 +/- 2 mmHg) (P less than 0.001) and was associated with higher pressures in the WKY (146 +/- 4 mmHg in the restricted WKY vs. 134 +/- 4 mmHg in the control WKY). In a parallel group of 24 SHRs and 24 WKYs fed one of three diets (2% Ca2+/1% Na+; 1% Ca2+/0.45% Na+; or 0.1% Ca2+/0.25% Na+), the heart (P < 0.05) and kidney (P = 0.08) weight of the SHRs varied depending on the diet at 20 wk of age. Low Ca2+ and Na+ intake was associated with increased heart weight (1.6+/-0.9 g) compared with the normal diet for SHR (1.51+/-0.07 g). Increased Ca2+ and Na+ intake was associated with a significantly (P = 0.05) lower heart weight in the SHR (1.37+/-0.03 g) and in the WKY (1.35+/-0.06 g) compared with their normal diet controls. These findings show one mechanism for the SHR's depressor response to supplemental dietary Ca2+ and, in part, explain the sodium dependence of calcium's cardiovascular protective effect.

Abnormal vitamin D metabolism, intestinal calcium transport, and bone calcium status in the spontaneously hypertensive rat compared with its genetic control.

Abnormalities of intestinal calcium absorption and the vitamin D axis in the spontaneously hypertensive rat (SHR) are controversial. The present report documents a reduction in circulating 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in the 12-14-wk-old male SHR with evidence of its functional significance. Both plasma 1,25(OH)2D3 and mucosa-to-serosa duodenal calcium flux (Jm-s), measured by the Ussing chamber, were significantly lower (approximately 60% of value in Wistar-Kyoto rats [WKY]) in SHR on both normal (1%) and low (0.1%) calcium diets than in corresponding control WKY. Low dietary calcium increased both 1,25(OH)2D3 and Jm-s by approximately 80% in SHR and WKY, with levels of both parameters rising in the SHR to levels found in the WKY under baseline conditions. The latter fact suggests the improbability of intestinal resistance to the action of 1,25(OH)2D3 in the SHR. Plasma 25-hydroxyvitamin D3 (25(OH)D3) was not significantly different between the strains. Intraperitoneal 1,25(OH)2D3 increased Jm-s in 12-14-wk-old SHR to levels observed in equivalent WKY. In 20-24-wk-old SHR, calcium deprivation was associated with significantly reduced Jm-s compared with equivalent WKY. Bone density and bone calcium content in 20-30-wk-old SHR were significantly reduced. In summary, we provide evidence that the SHR was unable to sustain appropriate circulating levels of 1,25(OH)2D3, an impairment which resulted in reduced duodenal calcium absorption.

Stem cells for mesothelial repair: an understudied modality.

Adhesions are bands of fibrous tissue that form between opposing organs and the peritoneum, restricting vital intrapleural and abdominal movement. They remain a major problem in abdominal surgery, occurring in more than three fourths of patients following laparotomy. Adhesions result when injury to the mesothelium is not repaired by mesothelial cells and can be viewed as scar tissue formation. The mechanism of mesothelial healing suggested the involvement of stem cells in the process. It has long been known that peritoneal wounds heal in the same amount of time regardless of size. Therefore, the mesothelium could not regenerate solely by proliferation and centripetal migration of cells at the wound edge as occurs in the healing of skin epithelium. Several studies suggest the presence of i) mesothelial stem cells that can differentiate into mesothelial cells and a few other phenotypes and/or ii) that mesothelial cells are themselves stem cells. Other studies have suggested that adult stem cells in the muscle underlying the peritoneum can differentiate into mesothelial cells and contribute to healing. Prevention of abdominal adhesions have been accomplished by delivery of autologous mesothelial cells and multipotent adult stem cells isolated from skeletal muscle. Adult stem cells from sources other than the serosal tissue offer an alternative treatment modality to prevent the formation of abdominal adhesions.

Rapid (10-minute) stimulation of rat duodenal alkaline phosphatase activity by 1,25-dihydroxyvitamin D3.

Recent reports have suggested that the action of calcitriol is much more rapid than previously thought. It is thus possible that some actions do not depend on de novo protein synthesis. A precise microdensitometric technique has been used to characterize the time course of the intestinal brush border alkaline phosphatase (AP) response of rat duodenal villi to the administration of calcitriol as AP activity has been shown to be dependent on the vitamin D status of the animal. The technique enables AP activity to be determined in situ without tissue disruption. After ip administration of 200 ng calcitriol to vitamin D-deficient male Wistar AF rats, a biphasic AP response was observed with an early peak within 1 h (0.068 +/- 0.011 vs. 0.101 +/- 0.003 integrated extinction (IE) min.micron 3 X 10(3), P less than 0.05) and a second at between 6 and 8 h (0.088 +/- 0.005 vs. 0.172 +/- 0.003 IE/min.micron 3 X 10(3), P less than 0.001). In a further experiment, the early response to calcitriol was reexamined with observations at 0, 10, 30, 45, and 60 min after administration of either calcitriol or vehicle (n = 5 pairs per time point). AP activity was significantly increased in the calcitriol group compared with the vehicle-treated group as early as 10 min after administration (0.132 +/- 0.003 vs. 0.151 +/- 0.005 IE/min.micron 3 X 10(3), P less than 0.02) and reached a peak 45 min after administration at which time AP activity was equal to that found in normal vitamin D-replete animals (0.193 +/- 0.003 vs. 0.192 +/- 0.002 IE/min.micron (3) X 10(3), P greater than 0.5). The speed of this response indicates it to be unlikely to depend on de novo protein synthesis.

Hyperparathyroidism and abnormal calcitriol metabolism in the spontaneously hypertensive rat.

Abnormalities of calcium metabolism and of its two principal regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol), have been reported in the spontaneously hypertensive rat (SHR). Reports of abnormal calcitriol metabolism in the SHR by several groups have not provided measurements of tissue calcitriol receptors. Similarly, few data are available as to the parathyroid status of the SHR. In the present study, circulating calcitriol levels and intestinal and parathyroid gland calcitriol receptor status were determined in male SHR and in Wistar-Kyoto (WKY) rats. Parathyroid status was investigated by determination of parathyroid gland mass together with tissue micromorphometry and by quantitative histology of bone as a measure of the biological action of parathyroid hormone. Circulating calcitriol levels were reduced in the 11-week-old SHR compared with the WKY rat (165 +/- 23 vs. 194 +/- 28 pmol/l, p less than 0.01, mean +/- SD). Calcitriol-free ratio was diminished and maximal specific binding capacity for calcitriol was increased in the SHR in parathyroid tissue (172 +/- 4.9 vs. 123 +/- 6.6 fmol/mg protein, p less than 0.01) and in intestinal mucosa with no change of receptor affinity. Plasma ionized calcium (1.29 +/- 0.05 vs. 1.45 +/- 0.35 mmol/l, p less than 0.05) and phosphate (1.5 +/- 0.26 vs. 2.4 +/- 0.03 mmol/l, p less than 0.05) were significantly lower in the SHR. Parathyroid gland mass was increased in the SHR (59 +/- 12 vs. 17 +/- 7 micrograms/100 g body wt, p less than 0.001) as a result of hyperplasia and not hypertrophy. Higher osteoclast numbers were observed in SHR bone (27.6 +/- 0.79 vs. 23.9 +/- 0.66 osteoclasts/mm2, p less than 0.01), suggesting increased parathyroid hormone activity. In summary, in the 11-week-old SHR we observed reduced circulating calcitriol levels together with increased tissue calcitriol receptor numbers, increased parathyroid gland mass, and histological evidence of hyperparathyroidism. It is possible that these abnormalities influence the development of hypertension in the SHR.

Chemotactic response of osteoblast-like cells to transforming growth factor beta.

Transforming growth factor beta (TGF-beta) was tested for its ability to stimulate a chemotactic response in two clonal rat osteosarcoma (ROS) cell lines, 17/2 and 25/1. TGF-beta stimulated dose-dependent chemotaxis in both cell lines. In serum-containing media, maximal response was seen at a concentration of 500 fg (10(-15)g)/mL for the ROS 17/2 cells and 25 fg/mL for the ROS 25/1 cells. In serum-free media, the maximal chemotactic response to TGF-beta occurred at 5 fg/mL for both the ROS 17/2 and 25/1 cells. TGF-beta was not mitogenic at these dosages. The results indicate that TGF-beta could act as a chemoattractant for osteogenic cells in both demineralized bone matrix induced osteogenesis and in normal bone remodeling.

Chemotactic response of mesenchymal cells, fibroblasts and osteoblast-like cells to bone Gla protein.

Bone gla protein (BGP) and decarboxylated bone gla protein (dBGP) were tested for chemotactic activity against stage 24 chick limb bud mesenchymal cells, chick embryonic muscle-derived fibroblasts, murine Balb/C 3T3 cells, and two lines of rat osteosarcoma cells, ROS-17/2.8 and -25/1. Both BGP and dBGP were potent chemoattractants for all the cell types except 3T3 cells. The dose response curves were bell-shaped, with maximal chemotactic response ranging from 5 pg/ml for ROS 25/1 cells to 10 ng/ml for the stage 24 limb bud cells. dBGP was equally potent a chemoattractant as BGP for all cell types tested indicating that the gamma-carboxylation of the glutamic acid residues is not required for chemotactic activity. Given this chemotactic capability, it is possible that BGP acts in bone remodelling by attracting osteogenic cells to the sites of bone resorption where BGP may be liberated or exposed.

Partial isolation and characterization of a chemotactic factor from adult bovine bone for mesenchymal cells.

Demineralized adult bone matrix has the capacity to initiate de novo ectopic endochondral bone formation 2-3 weeks following intramuscular implantation into suitable hosts. An early step in this process is the migration of mesenchymal cells to the implant site; these cells later differentiate into cartilage and bone. Adult bone has been shown to contain a number of bioactive factors, such as chemotactic factors for various cell types, including osteoblasts. We have used embryonic chick limb bud mesenchymal cells to construct an in vitro assay for testing chemotactic activity derived from bone matrix extracts. With a modified Boyden chamber, water-soluble components from a 4 M guanidinium chloride extract of demineralized adult bovine bone matrix were found to stimulate the directional migration of these chick embryonic limb bud mesenchymal cells as well as embryonic muscle-derived fibroblasts and cells derived from embryonic skin. The chemotactic activity was destroyed by treatment with heat (100 degrees C) or trypsin. Partial purification by molecular sieve chromatography suggested that the chemotactic factor(s) has a molecular weight of between 50,000 and 90,000. This factor can be separated from bone matrix-derived chondrogenic stimulating activity by either ion exchange or molecular sieve chromatography. These observations confirm that bone matrix contains a chemoattractant for mesenchymal cells that may be important for in vivo recruitment of cells as part of the process of ectopic bone formation or in cases of bone repair.

Repair of articular cartilage defects using mesenchymal stem cells.

Degeneration of articular cartilage in osteoarthritis is a serious medical problem. We have isolated a population of cells from the connective tissue of mammals termed mesenchymal stem cells (MSCs) for their apparent unlimited growth potential and their ability to differentiate into several phenotypes of the mesodermal lineage, including cartilage and bone. These qualities make them ideal candidates for cartilage repair. We isolated MSCs from adult rabbit muscle and cultured them in vitro into porous polyglycolic acid polymer matrices. The matrices were implanted into 3-mm-diameter full thickness defects in rabbit knees with empty polymer matrices serving as the contralateral controls. The implants were harvested 6 and 12 weeks postop. At 6 weeks, the controls contained fibrocartilage while the experimentals seemed to contain undifferentiated cells. By 12 weeks postop, the controls contained limited fibrocartilage and extensive connective tissue, but no subchondral bone. In contrast, the implants containing MSCs had a surface layer of cartilage approximately the same thickness as normal articular cartilage and normal-appearing subchondral bone. There was good integration of the implant with the surrounding tissue. Implantation of MSCs into cartilage defects appears to effect repair of both the articular cartilage and subchondral bone. Studies are ongoing to further characterize the use of MSCs for cartilage repair.

Epithelial abnormalities in intestine and kidney of the spontaneously hypertensive rat.

A variety of perturbations of calcium metabolism are reported to occur in the spontaneously hypertensive rat (SHR) compared to its genetic control the Wistar-Kyoto rat (WKY), including significant dysfunction of calcium handling by the proximal renal tubule of the SHR, resulting in impaired active calcium transport in the gut and an apparent renal calcium leak. We explored the intestinal and renal epithelia of 12- to 14-week-old SHR and WKY using electron microscopy. Biochemical comparisons of these transport epithelia included measurements of three vitamin D dependent cellular proteins and one structural protein: alkaline phosphatase, intestinal CaBP9K, renal CaBP28K, and villin expression. Electron microscopy demonstrated a patchy loss in microvilli in the SHR, accounting for approximately 10 to 15% of the total microvillar surface. In the kidney, morphological abnormalities were observed only in the proximal renal tubule. Again, there was patchy loss of microvilli from the brush border membrane. In SHR duodenal alkaline phosphatase activity was significantly reduced compared to the WKY (0.145 +/- 0.002 v 0.186 +/- 0.002 integrated extinction/min/micron 3 X 10(3) brush border (P less than .001). Duodenal CaBP9K and renal CaBP28K were significantly reduced in SHR compared to WKY. There were no differences in villin expression. These data are consistent with the previously characterized disturbances of active calcium transport in the intestine and inappropriate renal calcium leak in the SHR. While a possible link between these disturbances and hypertension remains to be determined, this study provides supportive evidence for a primary disturbance in cell calcium handling and transporting epithelia in this form of genetic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased duodenal enterocyte calcium flux rates in the spontaneously hypertensive rat.

We have previously reported serum 1,25(OH)2 vitamin D3 (calcitriol) and active transduodenal calcium absorption measured in the Ussing chamber to be reduced in 12- to 14-week-old male Okamoto-Aoki spontaneously hypertensive rats (SHR). In the present study, we compared rates of calcium influx and efflux in isolated duodenal enterocytes in SHR and corresponding controls, Wistar-Kyoto rats (WKY). The early (0 to 1 minute) and the late (1 to 15 minute) phase of calcium influx rates at 1.0 mmol Ca2+ in the incubation medium were lower in the SHR than in the WKY (mean +/- SEM): 1.93 +/- 0.22 v 2.85 +/- 0.41 nmol/mg protein/min, n = 8 and n = 7 experiments, respectively, P less than .05; and 0.334 +/- 0.025 v 0.488 +/- 0.059 nmol/mg protein/min, n = 14 pairs, P less than .01. The calcium efflux rate constant of the SHR was reduced: 34.3 +/- 1.4 v 51.9 +/- 1.4% per hour, n = 11 pairs, P less than .01. However, in the absence of sodium or the presence of ouabain (4.0 mmol) in the incubation medium, a decrease in this constant was observed in the WKY but not in the SHR. These data, at the cellular level, support our previous observation in intact tissue of reduced active transduodenal calcium transport in the 12- to 14-week-old SHR. Whether the primary defect in calcium transport involves the luminal or the basolateral membrane of the enterocyte, or whether both disturbances are due to a common primary perturbation cannot be deduced from the present experiments.

Loin pain and haematuria syndrome: a somatoform disorder.

Fifteen patients with the loin pain and haematuria syndrome (LPH) were compared with 10 patients with complicated renal stone disease referred to the same tertiary centre and matched for age, sex and duration of illness. LPH patients had a history of three times more medically unexplained somatic symptoms other than loin pain (p < 0.01) and a higher proportion took analgesics regularly (p < 0.01). The onset of pain was associated with an adverse psychologically important life-event in eight of the LPH patients but in none of the controls (p < 0.02). LPH patients more frequently recalled serious parental illness and disability in childhood (p < 0.001) than controls, and a higher proportion felt responsible for causing or alleviating parental illness or distress (p < 0.05). LPH subjects scored higher in the 'paternal care' dimension of the Parental Bonding Instrument (p < 0.05). No difference was found between LPH patients and controls in terms of current depression and anxiety but both groups exhibited high rates of lifetime depression. LPH patients expressed lower levels of anger and hostility (p < 0.002) than did controls. Our observations suggest that psychological factors are of major importance in the aetiology of LPH, which may represent a type of somatoform pain disorder.

Interrogative suggestibility in patients with conversion disorders.

We tested the hypothesis that increased interrogative suggestibility may contribute to the shaping and maintaining of conversions symptoms. Interrogative suggestibility was measured in 12 patients with conversion disorder and 10 control patients with confirmed neurological disease matched for age, premorbid intelligence, and as closely as possible in terms of their neurological symptoms to the patients with conversion disorder. Our observations do not support the contention that individual differences in interrogative suggestibility are of importance in the etiology of conversion disorders.

1,25-dihydroxycholecalciferol and parathyroid hormone in advanced chronic renal failure: effects of simultaneous protein and phosphorus restriction.

Vitamin D3 metabolites and immunoreactive parathyroid hormone (iPTH) were measured in sera obtained from subjects with advanced chronic renal failure (CRF) (creatinine clearance less than 10 ml/min) before and after 3 months on a diet very low in protein (less than 0.2 g/kg/day), phosphorus (less than 500 mg/day), and supplemented with a mixture of essential amino acids and ketoacid analogues of essential amino acids. iPTH and phosphate fell in all subjects (p less than 0.02). 1,25-dihydroxycholecalciferol (1,25[OH]2D3) fell in all but one of the subjects (p less than 0.02), while no significant change was seen in creatinine clearance or in serum 25-hydroxycholecalciferol (25[OH]D3) levels. A strongly positive correlation was found between initial serum levels of 25(OH)D3 and 1,25(OH)2D3 (r = 0.95, p less than 0.001). Thus in contrast with the reported effects of dietary phosphorus reduction in subjects with early and moderate CRF and in normal subjects, this regime was associated with decreased 1,25(OH)2D3 levels in subjects with advanced CRF.

Pluripotent mesenchymal stem cells reside within avian connective tissue matrices.

Recent studies have noted the presence of putative stem cells derived from the connective tissues associated with skeletal muscle, heart, and dermis. Long-term continuous cultures of these cells from each tissue demonstrated five distinct phenotypes of mesodermal origin, i.e. muscle, fat, cartilage, bone, and connective tissue. Clonal analysis was performed to determine whether these morphologies were the result of a mixed population of lineage-committed stem cells or the differentiation of pluripotent stem cells or both. Putative stem cells from four tissues (skeletal muscle, dermis, atria, and ventricle) were isolated and cloned. Combined, 1158 clones were generated from the initial cloning and two subsequent subclonings. Plating efficiency approximated 5.8%. Approximately 70% of the 1158 clones displayed a pure stellate morphology, while the remaining clones contained a mixture of stellate, chondrogenic- or osteogenic-like morphologies or both. When cultured in the presence of dexamethasone, cells from all clones differentiated in a time- and concentration-dependent manner into muscle, fat, cartilage, and bone. These results suggest that pluripotent mesenchymal stem cells are present within the connective tissues of skeletal muscle, dermis, and heart and may prove useful for studies concerning the regulation of stem cell differentiation, wound healing, and tissue restoration, replacement and repair.

Inhibition of epidural scar formation after lumbar laminectomy in the rat.

STUDY DESIGN: An animal model of laminectomy in rats was used to study scar tissue formation around the spinal cord. Dexamethasone, in controlled-release form, was tested in this system for its ability to decrease fibrous tissue formation. OBJECTIVES: The results were evaluated to determine whether dexamethasone in a biodegradable controlled-release vehicle could be used to limit scar tissue formation around the spinal cord after laminectomy. SUMMARY OF BACKGROUND DATA: Steroids can delay the formation of scar tissue. Continued treatment with dexamethasone results in various unacceptable side effects. Use of biodegradable controlled-release vehicles to deliver drugs may allow for prolonged low-dose treatment, concentrated at the surgical site, thereby avoiding side effects. METHODS: Forty-four Sprague Dawley rats underwent laminectomies and were treated with dexamethasone in one of two controlled-release vehicles or with vehicle alone. After 4 weeks, the rats were killed and histologic sections prepared from the spines were examined and graded by a pathologist. In addition, the dexamethasone preparations were introduced into Hunt-Schilling wound chambers, which were implanted in rats. Four weeks after implantation, the wound chambers were removed and the tissue inside was assayed for DNA and protein content. RESULTS: Dexamethasone acetate (Decadron, MSD, West Point, PA) significantly reduced the density of the scar tissue undermining the laminas. Steroids embedded in polymer did not change the scar formation in the back, but did decrease protein and DNA values in wound chamber tissues. CONCLUSIONS: Long-term release of small amounts of steroid from the polymer poly-carboxy-phenoxypropane does not appear to reduce scar at laminectomy sites but does decrease the protein:DNA ratio in wound chambers. In contrast, Decadron does not significantly alter the biochemistry of wound chamber tissue but does reduce scar in the back.

Differentiation factors induce expression of muscle, fat, cartilage, and bone in a clone of mouse pluripotent mesenchymal stem cells.

Growth factors have been used experimentally to accelerate wound healing by increasing scar tissue formation at a wound site. These studies suggest that stimulation of fibroblastic differentiation and proliferation are essential components of adult tissue repair. Recent studies report the presence of mesenchymal stem cells within granulation tissue and as connective tissue-resident stem cells. This suggests that mesenchymal stem cells as well as fibroblasts may contribute to wound healing and repair. To determine the potential for mesenchymal stem cells to contribute to nonfibrogenic tissue repair, a clonal population of murine mesenchymal stem cells was examined with dexamethasone, a general differentiation agent, and muscle morphogenetic protein, a specific differentiation-inducing agent. Dexamethasone induced the expression of phenotypic markers for fat, cartilage, and bone in the stem cells. Muscle morphogenetic protein induced the expression of mRNAs for the muscle specific regulatory genes MyoD1 and myogenin in these cells. These results suggest that pluripotent mesenchymal stem cells within connective tissue compartments and granulation tissue have the potential to contribute to functional tissue restoration, rather than contributing solely to fibrogenic scar tissue formation during tissue repair.

Auditory-verbal hallucinations and the phonological loop: a cognitive neuropsychological study.

A patient with continuous auditory-verbal hallucinations was studied, in comparison with two cases with a past history of similar hallucinations, from a cognitive neuropsychological perspective. This attempts to place hallucinations in the context of a normal cognitive process which has become disordered. The process in question is the phonological loop, equivalent to inner speech, derived from a model of short-term or working memory. A series of short-term memory tests, assumed to rely on the adequate functioning of the phonological loop, was administered, the results of which broadly conformed to a normal pattern of performance. It is concluded that verbal hallucinations cannot be regarded as involving the phonological loop directly. Other points in the short-term memory/language system at which verbal hallucinations could arise are discussed, as are suggestions for further research of this kind.

The impact of genital trauma on wounded servicemen: qualitative study.

BACKGROUND: Recent military operations in Afghanistan have resulted in considerable lower limb trauma. Associated with this trauma have been serious injuries to the genitalia. No previous study has looked at the effect of traumatic genital injury on the individual. This study expresses the impact of these injuries. METHODS: A qualitative evaluation, interviewing 13 male patients with extensive genital injuries, including 11 patients with orchidectomies. RESULTS: Patients attach a very high importance to their genital injury, rating this injury as having more impact than lower limb amputations. They also have a high expectation for the recovery of sexual function. Psychological outcomes are better when an individual's future fertility is known at an early stage. CONCLUSION: Better outcomes are achieved for the patient when psychological and surgical support if provided throughout the long treatment and recovery process It is important that every effort is made to preserve fertility right from the point of injury.