Dual function nitroimidazoles less toxic than RSU 1069: selection of candidate drugs for clinical trial (RB 6145 and/or PD 130908.

Following the toxicity and synthetic difficulties encountered with the hypoxic cell radiosensitizer RSU 1069, efforts have focused on development of a superior analogue. Two compounds, RB 6145 and PD 130908, have emerged from this program which overcome the instability and synthetic problems associated with RSU 1069 while retaining favorable biological activity. Both agents show comparable radiosensitizing activity to RSU 1069 following oral or i.p. administration to mice bearing the KHT or RIF-1 tumors. Sensitizing efficiency is about 10 X greater than that observed for misonidazole or etanidazole. Toxicity toward hypoxic tumor cells in vivo is demonstrated by clamping tumors (for 60 min) following administration of PD 130908 or RB 6145. Both are effective hypoxic cytotoxins, but less potent than RSU 1069. Systemic toxicity is substantially reduced following oral drug administration. Further, doses achievable following fractionated drug treatments are sufficiently high to produce significant levels of radiosensitization.     

TOTAL LARYNGECTOMY WITH PRIMARY VOICE RESTORATION

Forty-three patients were prospectively studied following tracheo-oesophageal puncture at the time of laryngectomy (primary voice restoration). Blom-Singer voice prostheses were used. The surgery was regarded as successful if a patient continued to use the voice prosthesis as the major means of communication with clear intelligibility 4 months after the operation. Using this criterion, the success in this series was 70%. No attempt was made to assess the quality of speech. Complications and causes of failure are discussed.     

Electrocardiographic hypertrophic patterns in hypertensive Nigerians.

We studied hypertrophic patterns in the electrocardiograms of 60 Nigerian hypertensives. Thirty were in heart failure and 30 without failure (matched for age and sex). Combined left ventricular and left atrial hypertrophy was the commonest finding occurring in 58.3%, followed by left ventricular hypertrophy alone in 30%. 76.7% and 40% had combined left ventricular and left atrial hypertrophy in the heart failure and the non-heart failure groups, respectively (P less than 0.02). Though these changes increased with increased blood pressure, the latter is similarly severe in both groups. 100% of patients in Class IV failure had combined left ventricular and left atrial hypertrophy. The 3 patients who had additional right atrial hypertrophy were in Class IV failure, 2 of whom died during follow-up. These changes are much more marked at presentation than reprots in caucasians and even in previous reports in Africans. The changes reflect the long-standing nature and severity of the hypertensive process, and point to the fact that the majority of hypertensives in this environment present rather late.     

Does the Farnsworth D15 test predict the ability to name colours?

Background: The Farnsworth D15 test is designed to categorise colour vision deficiency as severe or moderate. The level of difficulty of the test was set so that those who passed it should be able to recognise surface colour codes, such as those used for electrical wiring. The test is widely used to provide advice to patients with abnormal colour vision and is often used for occupational selection when reliable recognition of surface colour codes is required. However, there has been only one previous study of the correlation between performance at the D15 test and the naming of surface colour codes and there has been no study of whether a person who passes the D15 can reliably name surface colours. Methods: One hundred and two people aged 11 to 65 years with abnormal colour vision were recruited from consecutively presenting optometric patients and were asked to name the colours of fabric, paint and cotton thread samples. There were 10 colours in each class of material and the samples were presented in a large (five to 10 degree angular subtense) and small size (2.5 deg and a single thread). The errors made were compared to those made by an age‐matched control group of equal size with normal colour vision. Results: The correlations between the Farnsworth D15 colour confusion index and colour naming errors were 0.62 for the large stimuli and 0.73 for the small stimuli. Its sensitivity and specificity identifymg those who made more errors than the worst performing colour normal person were 0.80 and 0.69 (large stimuli) and 0.75 and 0.71 (small stimuli). A Nagel anomaloscope range of less than 35 scale units provides essentially the same sensitivity and specificity. Conclusions: About 40 per cent of those with abnormal colour vision can name the main colours correctly under good visibility conditions. The D15 test is an imperfect predictor of those who can name surface colour codes correctly but it does provide useful information for general counselling. It is not suitable as a single test for occupational selection because it will pass 20 per cent who cannot name surface colours correctly and fail 30 per cent who can. In occupations in which recognition of surface colour codes is of critical importance, it may be best not to select people with abnormal colour vision because of the lack of a colour vision test that is a perfect predictor of the ability to recognise surface colours.     

Breastmilk intake and growth in infants from two to ten months

Longitudinal measurements of breastmilk intake in 48 Cambridge infants showed that intake reached a peak of 824 g/24 h in boys and 741 g/24 h in girls in the third and fourth months, respectively. Regression analysis demonstrated that, in the early months, the infants' weight accounted for a major part of the variance in breastmilk intake. Infants in non-manual social classes received more breastmilk and started solids later than those in manual groups. In the early months weight gain showed a relative increase compared to growth standards, but later infancy was characterized by a progressive deceleration in weight and length gain. Adiposity, as measured by triceps skinfold thickness differed most markedly from growth charts and was only equivalent to the tenth standard centile at all ages. The lower skinfold thickness measurements are considered to be more appropriate to breastfed infants in general.     

CT-guided brachial plexus biopsy.

We describe a technique for conducting a CT-guided biopsy of the brachial plexus region, report two illustrative cases, discuss potential complications, and conclude that, in selected cases, biopsy of lesions in the region of the brachial plexus can be performed safely with CT guidance.     

Neonatal 6-hydroxydopa, but not DSP-4, elevates brainstem monoamines and impairs inhibitory avoidance learning in developing rats

The involvement of brain monoamines in learning and memory in developing rats was studied by comparing the effects of 3 different noradrenergic neurotoxin treatments. Two experimental groups of male Sprague-Dawley rat pups were injected systemically with 50 micrograms/g of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) either on the day of birth or on postnatal days 17-18. Rats in the third experimental group were injected systemically with 60 micrograms/g of 6-hydroxydopa (6-OHDOPA) on postnatal days 0 and 2. Control littermates received vehicle. The animals were trained on an inhibitory avoidance task on postnatal days 27-29 and tested for retention 24 h later. The drug treatments produced comparable depletion of norepinephrine in the hippocampus and frontal cortex. 6-OHDOPA, but neither DSP-4 treatment, significantly elevated brainstem concentrations of norepinephrine and serotonin. In addition, 6-OHDOPA, but not DSP-4, significantly impaired retention of the inhibitory avoidance task. The impairment did not reflect insensitivity to the footshock used in training: both neonatal drug treatments tended to lower, not raise, footshock thresholds, as measured by a flinch test. High affinity choline uptake was not affected by either neonatal drug treatment in any of the brain areas examined. Thus, the 6-OHDOPA-induced behavioral deficit did not involve altered acetylcholine function. The results implicate brainstem monoamines in the modulation of learning and memory during development.