Vitamin A utilization status in chronic alcoholic patients

The utilization status of vitamin A (retinol) (treated with oral retinol - 2500 I.U. daily (=250 micrograms) x 5 days - "OROVITE -7", Bencard, England) in 25 patients (M = 23, F = 2; mean age +/- S.D. = 43.88 +/- 12.67; range = 28-70 years), 3 out of 25 patients (12%) were found to be deficient in the vitamin and during treatment further improvement of the blood levels of the vitamin was observed in all except one elderly male patient (age 61 years) and the mean levels on admission (661.04 micrograms/l) was also slightly improved after treatment (662.84 micrograms/l). Night blindness, alcoholic liver disease and hypogonadism are commonly seen in chronic alcoholic patients. Falling plasma levels of the vitamin indicate exhaustion of its hepatic storage. It is therefore suggested that chronic alcoholics should be given vitamin A supplementation along with other polyvitamins during conventional detoxification therapy for ethanol withdrawal syndrome in order to prevent dangerous manifestations of hypovitaminosis A, such as night blindness, cancer, hypogonadism and alcoholic liver disease.     

Excitatory Connections Between CA1 Pyramidal Cells Revealed by Spike Triggered Averaging in Slices of Rat Hippocampus are Partially NMDA Receptor Mediated

Spike triggered averaging was used to record local circuit connections between pairs of CA1 pyramidal neurons in isolated slices of rat hippocampus. Of 795 pairs of neurons tested, six were connected. These epsps were only partially blocked by 2-amino-5-phosphonovalerate (AP-5), which decreased the amplitude and half width of the epsp, but did not affect the early rising phase. In contrast, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked all phases of the epsp and combinations of AP-5 and CNQX blocked the epsp almost entirely. These results indicate that these epsps were mediated by both N-methyl-d-aspartate (NMDA) and non-NMDA excitatory amino acid receptors. Moreover, they exhibited a voltage relation typical of neuronal responses to NMDA, increasing in amplitude and duration as the postsynaptic cell was depolarized. These epsps were brief (10 - 90% rise time < 5 ms, width at half amplitude < 20 ms), indicating a proximal location. Increasing presynaptic firing rate (1 - 4 spikes/s) reduced average epsp amplitude by almost 50%. When epsps were evoked by pairs of spikes (interval 3 - 25 ms), a large response to the first spike precluded a large response to the second. No evidence for selective enhancement of the NMDA receptor component by paired spike activation was found. It is concluded that a significant NMDA receptor mediated input to CA1 is provided by local circuit CA1 - CA1 connections and that these synapses can be demonstrated under control conditions.     

Transformation of a partial nopaline synthase gene into tobacco suppresses the expression of a resident wild-type gene

A portion of the nopaline synthase gene under the control of the cauliflower mosaic virus 35S promoter was used to transform a tobacco plant that had previously been transformed with a wild-type nopaline synthase (nos) gene. Unexpectedly, in all nine primary transformants tested the wild-type nos expression was virtually completely suppressed. In contrast, plants transformed with the control vector DNA, which differed only in the absence of the partial nos gene, did not show any inhibition of nos expression. Progeny plants were analyzed for the stability of the gene-silencing phenotype. All of the progeny that carried both the wild-type and partial nos genes had no detectable nopaline synthase activity. In addition, wild-type nos mRNA could not be detected in these plants. In most plants in which the wild-type gene was segregated away from the partial nos gene, wild-type levels of activity were detected. Although DNA methylation has been shown to be correlated with a decrease in promoter activity in plants, none of the progeny appeared to carry a methylated nos promoter. The underlying mechanism causing this gene suppression phenomenon is unclear at this time.     

Comparative pharmacokinetics of co-trifamole and co-trimoxazole to `steady state' in normal subjects

1 The plasma and urine concentrations of trimethoprim (TMP) and sulphonamide obtained using co-trimoxazole and co-trifamole (TMP and sulphamoxole) were estimated in 10 patients in a two way cross-over study using the manufacturers' recommended dosage schedules.

2 The pharmacokinetics of TMP using either preparation were comparable with those reported elsewhere; as were the kinetics of sulphamethoxazole. The values obtained for sulphamoxole, not previously reported, were t_½ 8.0 ± 2.8 h, k_el 0.096 ± 0.031 h^-1, CL_s 0.9 ± 0.4 1h^-1 and V_d 9.4 ± 2.01.

3 Studies in plasma showed sulphamoxole to have a lower volume of distribution than sulphamethoxazole. The half-lives of the two did not differ significantly; steady state plasma concentrations were achieved more rapidly (25 h) for co-trifamole than for co-trimoxazole (49 h) as a result of the differences in recommended dosage schedule.

4 Differences in urinary concentration of TMP and sulphonamide obtained using the two preparations were a reflection of the dosage regimens rather than the pharmacokinetics of the individual drugs. Urinary concentrations of TMP greatly exceeded the MIC for sensitive organisms in all cases. Sulphonamide concentrations fell below the MIC for both drugs and in neither case were optimum synergistic ratios obtained in urine.

5 The figures obtained suggest that the use of sulphamoxole offers no advantage over sulphamethoxazole so far as the plasma and urinary concentrations are concerned, and suggest that in the treatment of urinary tract infections the necessity for combination therapy with TMP and a sulphonamide is open to question.

     

Observer variation in the interpretation of lower limb venograms.

After agreeing on diagnostic criteria and after a pilot study, two experienced radiologists twice independently reviewed 40 lower limb venograms performed by a standard technique in patients suspected or known to have venous thrombosis. The observers reviewed 20 examinations at a time, their analysis requiring separate identification of 11 major veins. At each site observers stated whether thrombus was "absent," "doubtful," "presumed," or "definite," or declared "no opinion possible." They then rediscussed criteria of diagnosis and, using the same experimental design, examined another 40 venograms. To correct for agreement expected by chance, data were analyzed by using the kappa statistic. In general, levels of agreement were higher than those reported for many other clinical and radiologic investigations, probably because of refinement of criteria after the pilot study. Nonetheless, observers disagreed about the probable presence or absence of thrombus at some site in the limb in about 10% of examinations. Observer variation should be considered when venography is used as a reference standard to evaluate other methods of diagnosing thrombi.     

Intermittent peritoneal dialysis in the treatment of end-stage renal failure.

Our experience of 54 patients with end-stage renal failure, who were treated with intermittent peritoneal dialysis and compared with patients maintained by haemodialysis over the years 1972 to 1978, has been reviewed. All patients received peritoneal dialysis for more than six weeks. The total experience was 32.8 patient dialysis-years, 48% as home dialysis. Peritoneal dialysis was used as an interim procedure in 19 patients who were waiting for haemodialysis. However, in 35 patients (particularly in the very young and elderly, and in situations of poor social support), recurrent peritoneal dialysis was chosen as the definitive dialysis therapy. Dialysis was assessed as "adequate" in all, but two, patients. The major complication of peritoneal dialysis was peritonitis, although its over-all incidence of 1.31 episodes per patient dialysis-year was low. An attack of peritonitis occurred every nine months of patient exposure, though the incidence of bacterial peritonitis averaged only once every 26 months. Fifty per cent of patients never had an episode of peritonitis. Intermittent peritoneal dialysis was associated with greater morbidity and mortality than haemodialysis, perhaps due, in part, to the older age of the peritoneal dialysis group. Intermittent peritoneal dialysis is a valuable adjunct to haemodialysis and transplantation in the treatment of end-stage renal failure.     

Acupuncture analgesia: an experimental investigation.

A study was designed to establish whether acupuncture has any analgesic properties beyond those of suggestion. In three one-hour experimental sessions the increases in detection thresholds and tolerances for thermal pain at six body locations on 12 subjects were compared. A control session (without needles) was followed by one session in which electrically stimulated needles were inserted in accord with Chinese practice, and another in which the needles were inserted to avoid all recognised acupuncture "points." Acupuncture was significantly more effective than suggestion in raising overall body pain thresholds but just below significance for tolerances. A significant disproportionate effect on the epigastrium, predicted by the choice of acupuncture points, was found for tolerances but not thresholds.     

Anti-tumour immunity in malignant melanoma assay by tube leucocyte adherence inhibition.

Tumour antigen-induced inhibition of leucocyte adherence was modified for use in glass test tubes (Tube LAI assay) for the study of cell-mediated anti-tumour immunity to human malignant melanoma. Peripheral blood leucocytes (PBL) of 20 out of 25 patients (80%) with active malignant melanoma responded to an extract of malignant melanoma with LAI, whereas only 4-5% of 475 control subjects showed a response. The malignant melanoma patients reacted to both allogeneic and autologous extracts of malignant melanoma which indicates a common cross-reacting antigen. Malignant melanoma patients did not respond to unrelated tumour extracts. The LAI was mediated by PBL (monocytes) "armed" with cytophilic anti-tumour antibody specific for the sensitizing tumour antigen. The anti-tumour response of the malignant melanoma patients was dependent on the stage of the cancer, and 11 out of 13 Stage I patients had a positive NAI, whereas patients with disseminated cancer had decreased response. The diminished LAI in patients with large tumour burdens appeared to be the result of release of tumour antigen systemically. Also, surgery and chemotherapy depressed LAI. Although LAI was depressed after surgical excision of the cutaneous melanoma, most patients showed LAI 1-3 months later. Tumour-free melanoma patients monitored for one year by the Tube LAI assay showed a decline in their anti-tumour immunity 5-6 months after surgery. The NAI was low or negative after the 8th post-surgical month in tumour-free patients. Patients with residual malignant melanoma showed persistent or recurrent LAI after the 8th post-surgical month. LAI reactivity monitored after "curative" surgery for malignant melanoma may assist in determining whether the patient is tumour-free or has a recurrence.     

The diets of preschool children in Newcastle upon Tyne, 1968-71.

1. Ninety-one families containing 140 children under 4 years of age at enrolment were studied. At 1-monthly intervals, the children were weighed and measured and qualitative information about feeding habits was obtained. Weighed dietary surveys for periods of 5 d were made at approximately 8 months, 3 years, and 5 years of age; there were forty-six failures in 260 surveys attempted. 2. At the four specified ages, mean energy intakes were 3-75, 5-03, 5-82 and 6-75 MJ (896, 1203, 1392 and 1613 kcal)/d respectively. At 8 months, milk products provided on average, 43% of the total energy intake, and commerical baby foods provided 17%. These values decreased to 21 and 2% respectively at 20 months and there was little further change therafter. 3. Average intake of energy and of most nutrients met recommended intakes (Department of Health and Social Security, 1969). Iron intakes were marginal, and vitamin D intakes were low. 4. The energy intake of boys was significantly higher than that of the girls at 3 years of age, but the boys were not significantly heavier. The energy intake of children from "manual-worker" families was higher than that from "non-manual" families. Similarly, the energy intake of children from larger families was higher than that of children from smaller families. 5. Energy intakes were correlated with body-weights and with rates of gain in weight. Irrespective of body-weight, "big eaters" at 20 months tended to be "big eaters" at 3 years also.