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.     

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.     

Wavelets of excitability in sensory neurons

We have investigated variations in the excitability of mammalian cutaneous mechanoreceptor neurons. We focused on the phase dynamics of an action potential relative to a periodic stimulus, showing that the excitability of these sensory neurons has interesting nonstationary oscillations. Using a wavelet analysis, these oscillations were characterized through the depiction of their period as a function of time. It was determined that the induced oscillations are weakly dependent on the stimulus frequency, and that lower temperatures significantly reduce the frequency of the phase response. Our results reveal novel excitability properties in sensory neurons, and, more generally, could prove significant in the deduction of mechanistic attributes underlying the nonstationary excitability in neuronal systems. Since peripheral neurons feed information to the CNS, variable responses observed in higher regions may be generated in part at the site of sensory detection.     

Human papovavirus in a routine urine specimen of a four-year-old boy

Cellular changes produced by viruses can be readily identified using light microscopy and Papanicolaou stain of a fixed specimen. These findings can then be confirmed by viral culture and/or electron microscopy studies. Human polyomavirus, common in transplant recipients or otherwise immunocompromised patients, is one virus that can be identified using these methods. The following is a case study of a 4-yr-old boy with no known immune impairment who exhibited human papovavirus (polyomavirus) on a routine urine examination. The diagnosis was confirmed by electron microscopy.     

Segmental reflexes mediated by joint afferent neurons in cat knee

1. Reflex effects mediated by knee joint afferent neurons were tested using the electrically evoked monosynaptic reflex in motoneurons innervating muscles which act about the knee. 2. Joint afferents were excited using small extension movements of the knee, stimuli which have been shown to be effective in activating a large fraction of the myelinated fibers in joint nerves. Because of the variability of reflex responses observed by others under similar experimental conditions, experimental control and data collection were done automatically under computer control. Large numbers of trials were presented in random sequence, and the resulting data were sorted and averaged. 3. Positive feedback was observed in both knee extensor (vasti) and knee flexor (posterior biceps-semitendinosus (PB-ST)) motoneuron populations. Vasti motoneurons were excited, and PB-ST motoneurons were inhibited by knee extensions when the posterior articular nerve (PAN) was intact; these effects were lost or substantially reduced when the PAN was cut. 4. Using knee extension stimuli, no reliable reflex effects were observed which could be attributed to afferents in medial articular nerve.