Silicon and aluminium interactions in haemodialysis patients.

BACKGROUND: Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity. METHODS: We measured serum aluminium and silicon levels from haemodialysis patients from four different centres. RESULTS: Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) micromol/l when serum silicon was less than 150 micromol/l, and lower, 1.1 (0.2-2.8) micromol/l when serum silicon levels were greater than 150 micromol/l (P = 0.03). CONCLUSIONS: In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.

Destabilizing effect of proline substitutions in two helical regions of T4 lysozyme: leucine 66 to proline and leucine 91 to proline.

A class of temperature-sensitive (ts) mutants of T4 lysozyme with reduced activity at 30 degrees C and no activity at 43 degrees C has been selected. These mutants, designated "tight" ts mutants, differ from most other T4 lysozyme mutants that are active at 43 degrees C, but only manifest their ts lesion by a reduced halo size around phage plaques after exposure of the growth plates to chloroform vapors. For example, in the series of T4 lysozyme mutants at position 157, the original randomly selected mutant, T1571, is the least stable of the series, yet, apart from the halo assay and subsequent in vitro protein stability measurements, this mutant is indistinguishable from wild type (WT) even at 43 degrees C. Two mutants were identified: L91P and L66P. Both insert proline residues into alpha-helical regions of the WT protein structure. The stabilities (delta delta G) as determined by urea denaturation are 8.2 kcal/mol for L91P and 7.1 kcal/mol for L66P. CD spectra indicate that no major conformational changes have occurred in the mutant structures. The structures of the mutants were modeled with a 40-ps molecular dynamics simulation using explicit solvent. For L91P, the reduction of stability appears to be due to an unsatisfied hydrogen bond in the alpha-helix and to a new buried cavity. For L66P, the reduction of stability appears to be due to a disruption of the interdomain alpha-helix, at least two unsatisfied hydrogen bonds, and a newly formed solvent-filled pocket that protrudes into the hydrophobic core, possibly reducing the stabilizing contribution of a partially buried intrachain salt bridge.

Poisonous snakebite in Utah.

A retrospective study was done of poisonous snakebite in Utah to determine the current epidemiology and scope of treatment, reviewing emergency department logs and other sources statewide for a 69-month period. Of 61 cases of poisonous snakebite identified, 13 occurred in snake hobbyists or venom laboratory personnel and were considered nonaccidental, and 48 were inflicted by native noncaptive snakes. These bites were considered accidental, and all were presumed to be from rattlesnakes. Nearly three fourths of the victims were male, ranging in age from 2 to 56 years (mean, 22 years). Most accidental bites occurred in areas of high human populations, during the summer months, in the afternoon or evening hours, and during recreational activities. Of the 48 bites, 11 (23%) were provoked. Two thirds of bites were on the upper extremities, and a third were on the lower extremities. More than half of the victims had no first-aid treatment recorded. Of those who did receive first aid, many were subjected to possibly harmful treatments, including tourniquets and ice application. The median time to a hospital was 68 minutes, with a range of 15 to 440 minutes. Swelling and discoloration were the most common signs and pain and paresthesia the most common symptoms. Half the bites resulted in minimal or no envenomation, 17 (35%) produced moderate envenomation, and 6 (12%) severe envenomation. Most patients with moderate or severe envenomation received antivenin, but the dosages given were usually less than recommended dosages. Five patients received surgical treatment based on clinical findings. One child died in a snake-handling incident. Long-term morbidity was unknown due to lack of follow-up. The Utah Poison Control Center was poorly utilized as a reporting and informational resource.

Aluminium chelation therapy in dialysis patients: evidence for inhibition of haemoglobin synthesis by low levels of aluminium.

To investigate the possibility that aluminium may exacerbate anaemia in dialysis patients with only modest aluminium accumulation, 15 patients whose exposure to aluminium had been low were treated for three months with the aluminium chelating agent desferrioxamine, 30 mg/kg intravenously at the end of each dialysis session. Serum aluminium concentrations before treatment were 5-125 micrograms/ml. After one month of desferrioxamine, serum aluminium (including the chelate) had risen from 54.6 (SEM 11.2) to 167.0 (27.5) micrograms/l; and after three months haemoglobin had risen from 8.46 (0.70) to 10.43 (0.80) g/l. Mean cell volume and mean cell haemoglobin concentration also increased significantly. The maximum rise in haemoglobin correlated with the patients' aluminium burden as estimated by the mean serum aluminium concentration after one month of desferrioxamine therapy (r = 0.85). The greatest response to desferrioxamine occurred in patients with a baseline serum aluminium of 15-75 micrograms/l (mean increase in haemoglobin 38%). The results indicate that even the modest aluminium accumulation found in most dialysis patients has a pronounced inhibitory effect on haemoglobin synthesis. The possible toxic effect of aluminium should be considered in all anaemic dialysis patients.

Residual renal function in hemodialysis patients may protect against hyperaluminemia.

We investigated 106 home hemodialysis patients whose mean [+/- SEM] serum aluminum (Al) concentration was 60.9 +/- 4.1 micrograms/liter. Serum Al concentration was inversely related to daily urine output (r = -0.52, P less than 0.001). Urine volume and measurements of Al exposure were included in a multivariate analysis of serum Al concentration in the 62 patients whose urine output was greater than 10 ml/day. The multiple correlation coefficient (r) was 0.70 (P less than 0.001) and the percentage contributions to r2 (indicating the relative importance of each factor) were: urine output 57%, oral Al intake 36%, total dialysis hours 7%. The additional contribution from cumulative water Al was negligible. In a subgroup of 26 patients with a urine output exceeding 10 ml/day, urinary Al excretion averaged 15.4 micrograms/day, and renal Al clearance and serum Al concentration were inversely related (r = -0.69, P less than 0.001). We conclude that Al-containing phosphate binders were a more important source of Al than was dialysate in these patients and that residual renal function can reduce the severity of hyperaluminemia in hemodialysis patients.

Homozygosity for the delta-chain variant haemoglobin A2' (HbB2) (delta 16 Gly----Arg).

A healthy 20-year-old woman, belonging to the Kgalagadi tribe of Botswana, has been found to possess a variant Haemoglobin A2 as her only minor haemoglobin component. Fingerprinting and amino-acid analysis have shown that it is Haemoglobin A2' (delta 16 Gly----Arg). The one parent available for study is heterozygous for the Hb delta A2' allele and the variant haemoglobin accounts for 3% of the total haemoglobin in the proband. It is reasoned that the proband is, therefore, homozygous for the Hb delta A2' allele. No haematological abnormalities were evident.

Haemoglobin J Rovigo 53 alpha (E-2) aspartic acid alanin.

The case under examination is an example of a family with Hb J Rovigo interacting with beta thalassemia. Such hemoglobin has the same mobility as J haemoglobin, and the analysis of amino acids showed it to be a variant of the alpha 53 (E2) Alanine-Aspartic chain. The percentage of haemoglobin ranged from around 22.7 to 30.5%.

Mechanisms of ampicillin resistance in Haemophilus influenzae from respiratory tract.

13 of 100 consecutive isolates of Haemophilus influenza obtained from respiratory specimens over the six months to June, 1979, had diminished sensitivity to ampicillin. 6 of the 13 strains produced beta-lactamase, whilst the remaining 7 had no evidence of this enzyme, either in whole cells or in extracts prepared by sonication. The minimum inhibitory concentration of ampicillin for the penicillinase-negative strains ranged from 1 mg/l to 8 mg/l on repeated testing with a carefully controlled agar-dilution technique. The findings contrast strongly with those of earlier surveys of the sensitivity of respiratory strains of H. influenzae to ampicillin and confirm the existence of two mechanisms of resistance to ampicillin in the species.

A new arthrogryposis syndrome with facial and limb anomalies.

A new familial syndrome of facial and limb anomalies was shown in a 4-month-old girl. Small mouth and jaw with limited jaw movement were seen in infancy, with growth to relatively normal size and movement in adulthood, but with a persistent, deep, horizontal depression just above the chin. Mild short stature and microcephaly as well as large ears with lack of the anthelix were present in family members. Severe flexion contractures of the hands and feet were present and led to subluxation of fingers and club feet in the most severely affect child. Marked variability among family members was seen, but a dominant inheritance seems likely.