Improving the safety and tolerability of local anaesthetic outpatient transperineal prostate biopsies: A pilot study of the CAMbridge PROstate Biopsy (CAMPROBE) method.

OBJECTIVES: The aim of this study was to pilot the use of a bespoke device (CAMPROBE, the CAMbridge PROstate Biopsy) to enable routine outpatient free-hand local anaesthetic (LA) transperineal prostate biopsies. MATERIALS AND METHODS: The CAMPROBE prototype was designed and built in our institution. Men on active surveillance due prostate resampling were invited to have a CAMPROBE biopsy as an alternative to repeat transrectal ultrasound-guided prostate biopsies (TRUSBx) as part of an approved trial (NCT02375035). Biopsies were performed using LA infiltration only, without sedation or additional analgesia. Patient-reported outcomes were recorded at day 0 and 7 using validated questionnaires and visual analogue scales (VAS). Complications were recorded prospectively. RESULTS: Thirty men underwent biopsies with a median of 11 cores taken per procedure (interquartile range 10-12). There were no infections, sepsis or retention episodes. Haematuria and haematospermia occurred in 67% and 62% of patients, which are similar to rates reported for TRUSBx. Mean VAS for pain (0-10 scale) was less than 3 for every part of the procedure. All 30 men described the procedure as tolerable under LA. In total, 26/30 (86.7%) men expressed a preference for a CAMPROBE procedure over TRUSBx and a further 3 (10.0%) would have either. CONCLUSIONS: In this small pilot study, the CAMPROBE device and method appears to be a safe, simple and well-tolerated out-patient transperineal replacement for TRUSBx. A major new National Institute for Health Research grant will allow its further development from a prototype to a single use, low-cost disposable device ready for multi-centre testing. LEVEL OF EVIDENCE: 1b: individual cohort study.

High prevalence of undiagnosed and severe chronic obstructive pulmonary disease at first hospital admission with acute exacerbation.

Chronic obstructive pulmonary disease (COPD) is a common cause of acute medical hospital admission, and the prevalence of undiagnosed COPD in the community is high. The impact of undiagnosed COPD on presentation to secondary care services is not currently known. We therefore set out to characterise patients at first admission with an acute exacerbation of COPD, and to identify potential areas for improvement in earlier diagnosis and further management. A retrospective case review of patients first admitted to a district teaching hospital with an acute exacerbation of COPD over a 1-year period was carried out. Forty-one patients with a first admission with an acute exacerbation of COPD were identified, 14 (34%) of whom had not been previously diagnosed and were diagnosed with COPD as a result of the admission. At presentation, this group of patients had severe disease, with mean (SD) FEV(1) 1.02 (0.32) L, and a respiratory acidosis in eight (20%) patients, even though this was their first admission for an acute exacerbation of COPD. Missed potential opportunities to intervene in community and inpatient management were identified, including earlier diagnosis, pre-hospital corticosteroid therapy, inpatient respiratory team input, provision of smoking cessation advice and consideration of pulmonary rehabilitation. Patients with a first hospital admission with an acute exacerbation of COPD frequently have severe disease at presentation. Despite having severe disease, a diagnosis of COPD had not been made in the community prior to admission in one-third of patients. Future work should be directed at earlier identification of patients who are symptomatic from COPD and ensuring that the interventions of proven benefit in COPD are systematically offered to patients in both primary and secondary care.

The effects of self-reinforcement and peer-reinforcement on the practice of breast self-examination.

Four months after learning breast self-examination (BSE), 169 sorority women assigned to one of three conditions (No Reinforcement, Self-Reinforcement or Peer-Reinforcement) were compared on BSE frequency subsequent to the training. Participants in both of the reinforcement conditions had agreed to a specified reward after each month's BSE, which was either self-delivered (Self-Reinforcement condition) or delivered by a partner (Peer-Reinforcement condition). Analysis of covariance revealed a significant difference among conditions and a Newman-Keuls test demonstrated that participants in both reinforcement conditions reported more months of BSE than those in the No Reinforcement condition. Furthermore, anxiety during BSE training was negatively correlated with BSE during the follow-up period. These results suggest that BSE, like other behaviors, is influenced by perceived support or rewards and by anxiety, and that BSE intervention programs should be designed with these findings in mind.

Estimating the rate of externalization of gonadotrophin-releasing hormone receptors in ovine anterior pituitary cells in vitro.

We report an estimate of the rate of externalization of unstimulated receptors for gonadotrophin-releasing hormone (GnRH), and derive from this the turnover time of the unstimulated receptor. The binding of the GnRH antagonist [acetyl-D-pCl-Phe1,2,D-Trp3,D-Lys6,D-Ala10]-GnRH to dispersed sheep anterior pituitary cells was non-saturable at 37 degrees C. Further experiments showed that the binding had two distinct phases. We suggest that these phases correspond to the initial, saturable binding to existing plasma membrane receptors, followed by binding to receptors as they are inserted into the surface membrane. The two processes are temporally distinct, and can be inhibited independently by pharmacological manipulations. The initial phase was inhibited by treatments that could be expected to reduce the number of active receptors on the cell surface (preincubation of the cells for 30 min with 100 micrograms neuraminidase/ml or 50 mumol GnRH/ml), and was complete in less than 30 min after the addition of the antagonist tracer. The second phase occurred continuously in the presence of tracer, and was reduced or abolished by inhibitors of microtubule function (100 mumol vinblastine/l), protein synthesis (25 micrograms cycloheximide/ml), or energy metabolism (0.25 mmol 2,4-dinitrophenol/l). The rate of insertion of receptors into the plasma membrane was calculated from the rate of increase of the second phase of binding. The calculated rate implies a 100% turnover of unstimulated receptors every 150 min. In contrast, previously published estimates of the rate of internalization of the GnRH-receptor complex in the rat pituitary suggest that the stimulated receptor is turned over much faster.

Effects of modifiers of cytoskeletal structures on the dynamics of release of LH from sheep anterior pituitary cells stimulated with gonadotrophin-releasing hormone, K+ or phorbol ester.

This study investigated the importance of reorganization of cell components by cytoskeletal structures to the short-term dynamic changes in LH release from dispersed sheep pituitary cells in perifusion, when stimulated with different dynamic patterns of gonadotrophin-releasing hormone (GnRH). The changes in rate of LH release investigated were the initial response to GnRH, desensitization, change of dose-response during desensitization, and recovery of sensitivity between pulses of stimulation. Cytochalasin D and colchicine were used to modify microfilament and microtubule action respectively. To determine whether receptor movement after binding of agonist was involved in the altered responses, K+ and phorbol 12-myristate 13-acetate (PMA) were used as stimulants because they cause LH release independently of agonist-receptor interaction. After 3 and 48 h culture on dextran beads and 2-3 h incubation in the presence and absence of 2-48 mumol cytochalasin D/1, or 8 or 250 mumol colchicine/l, aliquots of collagenase-dispersed sheep pituitary cells were stimulated at 37 degrees C in tubes or in a multicolumn perifusion system with 850 pmol GnRH/1, 109 mmol K+/1 or 10 nmol PMA/1. Fractions of supernatant or effluent were collected at intervals and LH concentrations measured by radioimmunoassay. Control samples were treated in the same way but without stimulation. Maximal, reversible enhancement of LH release over the first 20 min following stimulation with all secretagogues was observed after incubation of cells in 6 mumol cytochalasin/l. Desensitization behaviour, the supramaximal response, and the ability of cells to recover sensitivity to repeated pulses of GnRH were not altered by this modifier of microfilament polymerization at 6 or 24 mumol/ml. Colchicine at 8 mumol/l caused no changes in LH release. At 250 mumol/l, colchicine reduced the initial response of cells to GnRH stimulation but its action at this relatively high level may not be specific; there was no other major change in desensitization patterns, nor recovery of sensitivity to pulsed GnRH stimulation. Each treatment affected cellular responses similarly before and after culture. From studying the details of the dynamics of the short-term responses of gonadotrophs, we conclude that transport of cell components involving microfilaments and microtubules is unlikely to be a major limitation on the rate of LH release during desensitization, the supramaximal response, or the recovery of sensitivity between pulses of GnRH. This suggests that biochemical reactions rather than physical translocation may be rate-limiting in these processes.(ABSTRACT TRUNCATED AT 400 WORDS)

Risk factors for atherothrombotic brain infarction in persons over 62 years of age in a long-term health care facility.

A history of systolic (greater than or equal to 160 mm Hg) or diastolic (greater than or equal to 90 mm Hg) hypertension, diabetes mellitus (fasting venous plasma glucose greater than or equal to 140 mg/dl), a history of cigarette smoking, fasting serum total cholesterol greater than or equal to 200 mg/dl and greater than or equal to 250 mg/dl, and obesity (greater than or equal to 20% above ideal body weight) were examined as risk factors for atherothrombotic brain infarction (ABI) in 144 men, mean age 81 +/- 8 years, and 391 women, mean age 82 +/- 8 years, in a long-term health care facility. ABI occurred in 33 of 144 men (23%) and in 68 of 391 women (17%), P not significant. A history of systolic or diastolic hypertension correlated with ABI in both men and women (P less than 0.001). Diabetes mellitus correlated with ABI in both men and women (P less than 0.001). A history of cigarette smoking correlated with ABI in men (P less than 0.02) but not in women. Serum total cholesterol greater than or equal to 200 mg/dl and greater than or equal to 250 mg/dl did not significantly correlate with ABI in men or in women. Obesity did not significantly correlate with ABI in men or in women. Systolic or diastolic hypertension, diabetes mellitus, and cigarette smoking are risk factors for ABI in elderly men. Systolic or diastolic hypertension and diabetes mellitus are risk factors for ABI in elderly women.

Effects of lithium and phorbol esters on the dynamics of LH release from dispersed sheep pituitary cells.

The possible involvement of polyphosphoinositides in the stimulation of LH release was investigated. Dispersed sheep pituitary cells were incubated in test-tubes, or perifused in columns, with gonadotrophin-releasing hormone (GnRH) and Li+, or with a phorbol ester, and the amounts and patterns of LH release over time compared. Treatment with Li+ (10 mmol/l), which is known to increase levels of inositol phosphates in gonadotrophs, was shown to have effects only on the responses of desensitized cells, significantly decreasing the rate at which the cells desensitize (P less than 0.005) and decreasing the response to supramaximal levels of GnRH stimulus (P less than 0.01). It is suggested that these effects could be due to increased levels of inositol monophosphate, inositol bisphosphate or inositol 1,3,4-trisphosphate. Responses to single or repeated pulses of GnRH at 18-, 30- and 60-min intervals were not significantly altered. Phorbol 12-myristate 13-acetate (PMA), an activator of the calcium and phospholipid-dependent protein kinase (protein kinase C), was specifically active in releasing LH with a half-maximal stimulating dose of approximately 3 nmol/l. Phorbol 12,13-diacetate, which is structurally similar to PMA but does not activate protein kinase C, did not release LH, except at high levels in freshly dispersed cells. The timing of PMA-stimulated LH release was similar to that for GnRH-stimulated release, and PMA was able to release greater amounts of LH than could GnRH. This suggests that activation of protein kinase C is likely to be important in the GnRH-stimulated release of LH from gonadotrophs.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors for coronary artery disease in persons older than 62 years in a long-term health care facility.

A history of smoking 5 to 60 cigarettes per day, hypercholesterolemia (fasting total serum cholesterol 200 mg/dl or more), history of systolic (160 mm Hg or more) or diastolic (90 mm Hg or more) hypertension, diabetes mellitus (fasting venous plasma glucose 140 mg/dl or more) and obesity (at least 20% above ideal body weight) were correlated with coronary artery disease (CAD) in 138 men (mean age 82 +/- 8 years) and 380 women (mean age 82 +/- 8 years) in a long-term health care facility. CAD occurred in 43 of 138 men (31%) and in 103 of 380 women (27%), difference not significant. A history of smoking 5 to 60 cigarettes per day significantly correlated with CAD in men (p less than 0.001) but not in women. Hypercholesterolemia significantly correlated with CAD in both men (p less than 0.001) and women (p less than 0.005). A history of systemic hypertension significantly correlated with CAD in women (p less than 0.001) but not in men. Diabetes mellitus did not significantly correlate with CAD in men or women but weakly correlated with CAD in men plus women (p less than 0.05). Obesity did not significantly correlate with CAD in men or women. Hypercholesterolemia, a history of smoking 5 to 60 cigarettes per day, and a history of systemic hypertension were considered major risk factors. Having 2 or 3 major risk factors correlated with CAD significantly better than having no or 1 major risk factor in both elderly men (p less than 0.001, p less than 0.01) and women (p less than 0.001).