PubMed Health⌕ Search

Biomedical subjects

I Johnston

Publications and source records attributed to I Johnston.

At least 19 recordsLinked to original sources
PubMed1992

SCM4, a gene that suppresses mutant cdc4 function in budding yeast.

The gene SCM4 encodes a protein which suppresses a temperature-sensitive allele of the cell division cycle gene CDC4 in Saccharomyces cerevisiae. SCM4 was cloned on a 1.8 kb BamHI fragment of yeast genomic DNA in the high copy-number vector pJDB207, which results in a 50- to 100-fold increase in the level of the 700 nucleotide SCM4 transcript in vivo. The SCM4 gene encodes a 20.2 kDa protein of 187 amino-acids with a clear tripartite domain structure in which a region rich in charged residues separates two domains of largely uncharged amino acids. Although the apparent allele specificity of cdc4 suppression suggests that the CDC4 and SCM4 proteins interact, disruption of SCM4 demonstrates that the gene product is not essential for mitosis or meiosis; however, it may be a member of a family of related, functionally redundant proteins.

Alleles↗
PubMed1992

Pituitary gigantism.

A case of pituitary gigantism resulting from a pituitary adenoma which secreted growth hormone is described. The patient was successfully treated by surgery, which led to the normalisation of endogenous growth hormone secretion. An acceptable final height was achieved with high dose intramuscular testosterone treatment.

Adenoma↗
PubMed1992

Paraneoplastic cerebellar degeneration. III. Cerebellar degeneration, cancer, and the Lambert-Eaton myasthenic syndrome.

We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non-Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum.

Aged↗
PubMed1992

Action to reduce road casualties.

Progress in road safety is reviewed with particular reference to radical measures that have proved beneficial in Australia. Community involvement in decision-making is vital if gains are to be made and sustained in this field.

Accidents, Traffic↗
PubMed1992

Heterotopic pregnancy associated with gamete intra-fallopian transfer.

Recent reports in the literature have focused on the increased risk of heterotopic pregnancy after the transfer of multiple concepti or oocytes. In an international collaborative patient registry between 1985 and 1989, 601 clinical pregnancies resulted from 2092 gamete intra-Fallopian transfer (GIFT) retrieval cycles. Five of the pregnancies were heterotopic (0.83%). After surgical intervention, all five cases of combined gestation resulted in live birth from intrauterine pregnancies. Routine vaginal ultrasonographic examination of the adnexa in patients who conceive after GIFT may help early diagnosis of heterotopic pregnancy. If the diagnosis is made early, conservative treatment may preserve the future fecundity of the patient and more intrauterine pregnancies may be salvaged.

Female↗
PubMed1991

The pseudotumor syndrome. Disorders of cerebrospinal fluid circulation causing intracranial hypertension without ventriculomegaly.

We report a series of eight cases that show a close resemblance to, but are not identical with, pseudotumor cerebri (PTC) as normally defined. The majority of these cases are characterized by raised intracranial pressure without ventriculomegaly. They include two cases of cranial venous outflow obstruction in which clinical or radiologic abnormalities precluded the diagnosis of PTC proper (cases 1 and 2); one case of chronic meningitis in which an abnormal cerebrospinal fluid (CSF) composition precluded the diagnosis of PTC (case 3); two cases without either papilledema or a measured increase of CSF pressure, which in other respects, particularly in response to treatment, resembled PTC (cases 4 and 5); and three cases of what is thought to represent an infantile form of PTC (cases 6 through 8). The purpose of the analysis of these cases is twofold. First, it is argued that these cases throw light on the mechanism of PTC itself, supporting a concept of a disturbance of CSF circulation in this condition, and that they are themselves illuminated by considerations of typical PTC. Second, the cases are used to frame a proposed classification of the pseudotumor syndrome aimed at broadening the diagnostic criteria applied currently to PTC. It is suggested that the pseudotumor syndrome has a single underlying mechanism (disturbed CSF circulation) and that recognition of this mechanism not only clarifies the pathophysiologic processes of PTC but also has important diagnostic and therapeutic implications.

Adolescent↗
PubMed1991

Calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome.

We have tested 36 patients with the Lambert-Eaton myasthenic syndrome for serum antibodies to voltage-gated calcium channels by using an immunoprecipitation assay with [125I] omega-conotoxin-labeled voltage-gated calcium channels extracted from a human neuroblastoma cell line, SKN-SH. Forty-four percent of these patients had significant levels of antibody (30-1,466 pM) compared with healthy control individuals (less than 15 pM). The incidence of positive sera in patients without associated small cell lung carcinoma (61%) was greater than in those patients with small cell lung carcinoma (28%). Results correlated strongly with results obtained using voltage-gated calcium channels extracted from the small cell lung carcinoma line, MAR5. Anti-voltage-gated calcium channel antibody titers did not correlate with disease severity across individuals, but longitudinal studies in 2 patients receiving immunosuppressive therapy showed a clear inverse relation between antibody titer and an electromyographic index of disease severity. The incidence of positive sera among patients with other neurological disorders was not significant, but 8 of 12 patients with rheumatoid arthritis or systemic lupus erythematosus had raised titers (30-82 pM). We conclude that the antibodies detected in this assay are heterogeneous and that some of them are likely to be implicated in this disorder of neuromuscular transmission. The assay should prove useful as an additional diagnostic aid in patients with Lambert-Eaton myasthenic syndrome.

Action Potentials↗
PubMed1991

Seronegative myasthenia gravis: a plasma factor inhibiting agonist-induced acetylcholine receptor function copurifies with IgM.

Anti-acetylcholine receptor antibodies cannot be detected by standard radioimmunoassay in 10 to 15% of patients with generalized myasthenia gravis (seronegative myasthenia gravis). We investigated the effect of seronegative myasthenia gravis plasma on 22Na+ flux through acetylcholine receptors and voltage-gated sodium channels in the human rhabdomyosarcoma cell line, TE671. Fourteen of 19 seronegative MG plasmas inhibited acetylcholine receptor 22Na+ flux; none inhibited voltage-gated sodium channel flux. The inhibitory activity was found in the IgG-depleted fraction, and copurified with IgM after gel-filtration chromatography. Inhibitory activity was absent from the plasma of 8 healthy control subjects and of 6 patients with the Lambert-Eaton myasthenic syndrome, but was present in the IgG-depleted plasma fraction of 4 of 6 seropositive patients with myasthenia gravis and all 5 patients with demyelinating polyneuropathy. We conclude that a low-affinity serum factor, probably an IgM antibody, found in a high proportion in patients with seronegative and those with seropositive myasthenia gravis may contribute to the muscle weakness in myasthenia gravis, but its role in these and other neuroimmunological disorders requires further investigation.

Autoantibodies↗
PubMed1991

A familial coincidence of pseudotumor cerebri and communicating hydrocephalus.

A family in which the mother and two of four daughters had a diagnosis of pseudotumor cerebri and one son developed communicating hydrocephalus is described. The other two daughters both have a long history of headaches but no signs of intracranial hypertension. The argument is advanced that there exists a defect of cerebrospinal fluid absorption common to pseudotumor cerebri and communicating hydrocephalus.

Adolescent↗
PubMed1991

Benign intracranial hypertension in childhood: a review of 23 patients.

Twenty-three patients with benign intracranial hypertension (BIH) were seen at the Royal Alexandra Hospital for Children, Sydney over an 18 year period to 1988. Age at presentation ranged from 6 months to 13 years and 5 months. The female to male ratio was 2.3:1. The aetiological factors (sometimes multiple) included: chronic middle ear infection, 30%; dural sinus thrombosis, 22%; head injury, 13%; Vitamin A overdosage, 4%; tetracycline exposure, 4%; and no apparent cause, 43%. Headache was the most common presenting symptom occurring in 91% of patients, followed by vomiting in 65% and blurred or double vision in 57%. Papilloedema occurred in 96% of patients, abducens palsy was noted in 48% and visual impairment in 45%. All patients improved clinically after treatment, one with lumbar puncture only. Of 17 patients treated with steroids, 10 patients recovered and seven patients went on to lumboperitoneal shunt. Two patients recovered with steroid and diuretic treatment. Of two patients initially treated with diuretics only, one recovered and one subsequently required a shunt. Only one patient was initially treated with a lumboperitoneal shunt. Three of the shunted patients had shunt block requiring revision. None had permanent visual loss or other significant sequelae. The visual prognosis of BIH in childhood is good. In view of the relatively high complication rate of steroids and shunting, a controlled comparison of steroid vs acetazolamide/diuretic therapy should be undertaken.

Adolescent↗
PubMed1990

What causes cryptogenic fibrosing alveolitis? A case-control study of environmental exposure to dust.

OBJECTIVE: To investigate the role of occupational and domestic exposure to dust in the aetiology of cryptogenic fibrosing alveolitis. DESIGN: Matched case-control study. SUBJECTS: 40 Patients with cryptogenic fibrosing alveolitis and 106 community controls matched for age and sex who responded to a questionnaire. MAIN OUTCOME MEASURE: Responses to self administered questionnaire asking about lifetime exposure to dust, animals, and smoke at home and at work. RESULTS: The patients with cryptogenic fibrosing alveolitis were more likely to report occupational exposure to metal dust (matched odds ratio 10.97 (95% confidence interval 2.30 to 52.4), p less than 0.001) or wood dust (2.94 (0.87 to 9.90), p = 0.08), to have worked with cattle (10.89 (1.24 to 96.0), p = 0.01), and to have lived in a house heated by a wood fire (12.55 (1.04 to 114), p = 0.009). A history of smoking and social class based on occupation were not significantly related to disease state. CONCLUSION: Environmental exposure to dust may be an important factor in the aetiology of cryptogenic fibrosing alveolitis.

Aged↗
PubMed1990

Rising mortality from cryptogenic fibrosing alveolitis.

OBJECTIVE: To determine the pattern of mortality ascribed to cryptogenic fibrosing alveolitis and to identify factors that might be important in the aetiology of the disease; and to assess the validity of death certification of the disease. DESIGN: A retrospective examination of mortality ascribed to cryptogenic fibrosing alveolitis in England and Wales between 1979 and 1988 with analysis, by multiple logistic regression, of independent effects of age, sex, region of residence, and social class as indicated by occupation on data for 1979-87; also a retrospective review of hospital records of patients certified as having died of cryptogenic fibrosing alveolitis in Nottingham and of the certified cause of death of patients known to have had the disease. MAIN OUTCOME MEASURES: Time trends in mortality nationally; effects on mortality of age, sex, and region of residence; validity of death certification in Nottingham. RESULTS: The annual number of deaths ascribed to cryptogenic fibrosing alveolitis doubled from 336 in 1979 to 702 in 1988, the increase occurring mainly at ages over 65. Mortality standardised for age for both sexes likewise increased steadily over the period. Deaths due to cryptogenic fibrosing alveolitis were commoner in men (odds ratio 2.24, 95% confidence interval 2.11 to 2.33) and increased substantially with age, being 7.84 (7.24 to 8.49) times higher in subjects aged much greater than 75 than those aged 45-64. Odds ratios of death due to cryptogenic fibrosing alveolitis adjusted for age and sex were increased in the traditionally industrialised central areas of England and Wales (p less than 0.02, maximum odds ratio between regions 1.25), but no significant increase in odds of death was found for manual occupations. Of 23 people whose deaths were registered in Nottingham as having been due to cryptogenic fibrosing alveolitis, 19 were ascertained from clinical records to have had the disease. Only 17 of 45 patients known to have had cryptogenic fibrosing alveolitis in life were recorded as having died from the disease. CONCLUSIONS: The diagnostic accuracy of death certification of cryptogenic fibrosing alveolitis is high, but the number of deaths recorded as being due to the disease may underestimate the number of patients dying with the disease by up to half. Mortality due to the disease is increasing, and the male predominance and regional differences in mortality suggest that environmental factors are important in its aetiology.

Adolescent↗
PubMed1990

Human chorionic gonadotropin to oocyte retrieval interval in in vitro fertilization--how critical is it ?

This study shows that modification of the hCG-oocyte retrieval interval from 34 1/2 hours to 37 hours in patients having IVF had no significant effect on the number or quality of oocytes retrieved or on the ultimate pregnancy rate. More consideration can therefore be given to other factors such as patient convenience when scheduling the timing of hCG administration.

Cell Separation↗
PubMed1990

Increasing the human menopausal gonadotropin dose--does the response really improve?

This study assesses the effects of attempts to optimize human menopausal gonadotropin (hMG) dosage in 271 patients who had at least two hyperstimulation cycles for in vitro fertilization or gamete intrafallopian transfer. In the first cycle, all patients received clomiphene citrate and hMG 150 IU/d. In the second cycle, the hMG dose was increased in 45% of patients to try to increase the egg yield. In spite of the increase, the population response was practically identical in both cycles. Median numbers of eggs retrieved (6 versus 6), no eggs retrieved (0.4% versus 1%), only one or two eggs retrieved (10% versus 10%), and canceled cycles (10% versus 10.7%). This suggests that increasing the hMG dosage above 150 IU does not increase the number of eggs retrieved. A poor response may be due to inherent differences in follicular development that cannot be overcome by increases in hMG dosage.

Dose-Response Relationship, Drug↗
PubMed1988

Intracranial arteriovenous malformations: an 11-year experience.

A consecutive series of 107 patients with an intracranial arteriovenous malformation who were considered for surgical treatment over the 11-year period between 1974 and 1985 is analysed. In 71 (66.4%) patients complete obliteration (which in some cases was combined with pre- or peroperative embolization) by surgery was attempted and was achieved in all but two patients. Five patients were treated by embolization alone and three patients by radiotherapy alone. Twenty-eight patients were managed conservatively for one of four reasons: an expectation of a good outcome without treatment (six patients); the refusal of recommended surgical treatment (five patients); poor condition at presentation (eight patients); or the risks of operative treatment were thought to be too great (nine patients). There was a 9.9% mortality in the surgically-treated series and significant morbidity in 16 (22.3%) patients. In all but two of these 16 patients, morbidity was related directly to the initial intracerebral haemorrhage. The one-year mortality in the group that did not undergo operation was significantly higher than in those patients who were treated surgically. Some general guide-lines for the management of intracranial arteriovenous malformations are proposed.

Adolescent↗