A review of approaches to 18F radiolabelling affinity peptides and proteins

Affinity peptide and protein‐ (APP) based radiotracers are an increasingly popular class of radiotracer in positron emission tomography (PET), which was once dominated by the use of small molecule radiotracers. Radiolabelled monoclonal antibodies (mAbs) are important examples of APPs, yet a preference for smaller APPs, which exhibit fast pharmacokinetics and permit rapid PET aided diagnosis, has become apparent. ¹⁸F exhibits favourable physical characteristics for APP radiolabelling and has been described as an ideal PET radionuclide. Notwithstanding, ¹⁸F radiolabelling of APP is challenging, and this is echoed in the literature where a number of diverse approaches have been adopted. This review seeks to assess and compare the approaches taken to ¹⁸F APP radiolabelling with the intention of highlighting trends within this expanding field. Generic themes have emerged in the literature, namely the use of mild radiolabelling conditions, a preference of site‐specific methodologies with an impetus for short, automated procedures which produce high‐yielding [¹⁸F]APPs.     

Retinal detachments in patients with AIDS and CMV retinopathy: a role for laser photocoagulation.

A retrospective review of all patients with a cytomegalovirus (CMV) related retinal detachment and HIV infection managed at the ocular immunology clinic at St Vincent's Hospital between January 1985 and June 1992 was performed. Over this period 142 patients with CMV retinopathy were managed and 17 eyes from 14 of these patients developed a retinal detachment related to CMV retinopathy. Fourteen eyes from 11 of these patients were treated surgically with combinations of laser photocoagulation, cryopexy, scleral buckling, vitrectomy, and silicone oil tamponade. The use of laser photocoagulation alone in five patients resulted in an excellent visual outcome. The majority of patients (90.9%) benefited from surgery in that vision was either stabilised or improved.     

Response of joint capsule neurons to axial stress and strain during dynamic loading in cat

1. Experiments were conducted to test the hypothesis that the responses of joint capsule mechanoreceptors better encode tissue stress or tissue strain. The experimental model was a small ligament from the cat knee capsule, which was stretched uniaxially in vitro. Experiments were done with either force or displacement as the controlled variable, and with steps, sinusoids, or pseudorandom Gaussian noise (PGN) as the input function. 2. The strength of coupling between neural discharge and both strain and stress was quantified during step experiments using linear correlation coefficients. The correlation between the frequency of neural discharge and stress was 0.93 +/- 0.09 (SD). The correlation between frequency of neural discharge and strain was -0.91 +/- 0.06. The magnitudes of these correlation coefficients were not significantly different. 3. The strength of coupling between neural discharge and both strain and stress during sinusoidal and PGN experiments was quantified by the use of an information theoretic statistic, transinformation. Out of 282 sinusoidal runs, transinformation between neural discharge and stress was significantly greater than transinformation between strain and neural discharge 241 times. Transinformation between strain and neural discharge was significantly greater 15 times. 4. During PGN experiments, transinformation between stress and neural discharge was greater than transinformation between strain and neural discharge in all 19 experimental runs. 5. Conditional transinformation between strain and neural discharge, given stress, was calculated for all sinusoidal and pseudorandom experiments. This statistic was greater than zero in 268 out of 289 experimental runs, indicating that a component of strain independent of stress is being signaled in the neural discharge.     

Evaluation of the effects of elastic compression in patients with postphlebitic limbs by laser-Doppler flowmetry

Laser-Doppler flowmetry has been used to study the skin microcirculation in 20 normal limbs and 80 limbs of patients with venous hypertension and leg ulceration due to deep venous reflux. It was found that limbs with venous hypertension had a high skin resting blood flow (BRF) and an impaired veno-arteriolar reflex (VR). There was a marked improvement in both BRF and VR after elastic compression for three weeks and an association between this improvement and the rate of healing of the leg ulcers. The results indicate that elastic compression may affect the microcirculation even though it does not alter the venous pressure measurements when the elastic stockings are removed.     

Femorodistal vein bypass graft stenoses

Eighty femorodistal in situ vein bypass grafts have been evaluated at 3-monthly intervals clinically, with ankle:brachial pressure indices (ABI), by intravenous digital subtraction angiography (IV DSA) and by Duplex scanning. Five grafts (6 per cent) failed in the perioperative period. Nineteen (25 per cent) of the remaining 75 grafts subsequently developed stenoses on IV DSA during the first 12 months. All angiographic stenoses were detected by Duplex scanning using velocity ratio criteria before the development of symptoms or a measurable decline in ABI, i.e. while non-haemodynamically significant. This technique involves scanning the entire length of the graft but allows even minor stenoses to be detected and progression of stenoses can be determined. At a mean follow-up of 12 months (3-18 months), four (7 per cent) of the fifty-six grafts without stenoses occluded. Eight (42 per cent) of the nineteen stenosed grafts either occluded or developed symptoms. None of the occluded grafts in this series could be salvaged. Non-haemodynamically significant vein stenoses can be detected non-invasively, occur frequently and are associated with graft failure.     

An open-label efficacy pilot study with pimecrolimus cream 1% in adults with facial seborrhoeic dermatitis infected with HIV

BACKGROUND: Seborrhoeic dermatitis (SD) is a common dermatosis in human immunodeficiency virus (HIV)-positive patients, many of whom do not respond satisfactorily to conventional topical treatments such as corticosteroids and antifungals. OBJECTIVE: A pilot study to investigate the efficacy and tolerability of pimecrolimus cream 1% in HIV-positive patients with facial SD. METHODS: In a single-centre study, 21 HIV-infected patients with mild to severe SD were treated twice daily with pimecrolimus cream 1% for 14 days. Thereafter, treatment was discontinued and patients followed up for 5 weeks. Skin involvement at baseline and on days 7, 14, 21, 35 and 49 was assessed using a four-point clinical score and digital photography. MAIN OUTCOME MEASURES: Efficacy and safety of pimecrolimus cream 1% treatment and incidence of relapse in the follow-up phase. Results Marked improvement was seen in clinical parameters at day 7, with >or= 90% patients clear of symptoms at day 14. Relapse was observed at day 35 but signs were milder than at baseline. All patients responded to therapy, despite their immunological status. Pimecrolimus did not alter CD4(+) and CD8(+) T-cell counts or viral load during the treatment period. CONCLUSION: Pimecrolimus cream represents a new, effective therapeutic option for facial SD in HIV patients.     

A closed loop microprocessor controller for treatment of hypertension after cardiac surgery

Hypertension after cardiac surgery is common and requires accurate control by carefully regulated infusions of drugs such as sodium nitroprusside. A microprocessor-based controller has been designed to close the loop between the blood pressure response and the infusion rate of a hypotensive drug. This system has been refined by computer simulation of the blood pressure response to sodium nitroprusside and by experience gained in using the controller in eleven patients in the early recovery period after cardiac surgery. The controller was able automatically to maintain blood pressure within 10% of a specified value. Provision of sophisticated safety features in automatic drug infusion controllers is essential for patient protection.