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Biomedical subjects

C Higgins

Publications and source records attributed to C Higgins.

At least 37 records · Page 2Linked to original sources
PubMed1995

Keratin 16 and keratin 17 mutations cause pachyonychia congenita.

Pachyonychia congenita (PC) is a group of autosomal dominant disorders characterized by dystrophic nails and other ectodermal aberrations. A gene for Jackson-Lawler PC was recently mapped to the type I keratin cluster on 17q. Here, we show that a heterozygous missense mutation in the helix initiation motif of K17 (Asn92Asp) co-segregates with the disease in this kindred. We also show that Jadassohn-Lewandowsky PC is caused by a heterozygous missense mutation in the helix initiation peptide of K16 (Leu130Pro). The known expression patterns of these keratins in epidermal structures correlates with the specific abnormalities observed in each form of PC.

Amino Acid Sequence↗
PubMed1995

An evaluation of the action plans of children with asthma.

OBJECTIVE: To assess the provision and use of action plans in children attending hospital because of asthma. METHODOLOGY: An interviewer administered a structured questionnaire to the parents of 279 children attending the Casualty Department, Outpatient clinics or admitted to hospital because of asthma, at two Level 3 teaching hospitals. RESULTS: Only 82 (29%) of the children attending hospital had a written action plan. The majority (57%) were devised by paediatricians and covered the salient aspects of care. However, indications for steroid use were included in only 28% of plans and only 37% of the action plans in children over 5 years incorporated the use of peak flow meters. CONCLUSIONS: Action plans are still under-utilized in children with asthma. General practitioners should be encouraged to consider the use of action plans for the group of children not already covered.

Adolescent↗
PubMed1994

Localization procedures in patients with persistent or recurrent hyperparathyroidism.

OBJECTIVE: To determine the accuracy of noninvasive and invasive localization studies in patients with persistent or recurrent hyperparathyroidism (HPT). DESIGN AND SETTING: Reoperations based on patients who were treated surgically for recurrent or persistent HPT at the University of California-San Francisco Hospitals from 1982 to 1993. PATIENTS: This study evaluated 174 localization studies performed in 152 patients before reoperation (110 women and 42 men). MAIN OUTCOME MEASURES: The accuracy of localization studies, including ultrasonography, thallous chloride T1 201-technetium Tc 99m pertechnetate scanning, technetium Tc 99m sestamibi scanning, magnetic resonance imaging, computed tomography, and selective venous catheterization, were evaluated, as were the results of parathyroid reoperations. RESULTS: A total of 174 consecutive reoperations were performed in 152 patients with HPT (persistent, 113; recurrent, 39; mean age, 54 years; range, 21 to 88 years). One hundred thirty-three patients had primary HPT, 15 had secondary HPT, and four had tertiary HPT. Overall, 141 (93%) became normocalcemic, two (1%) became hypocalcemic, and nine (6%) remained hypercalcemic. Abnormal parathyroid glands at reoperation were situated in a normal location in 77 cases (44%), in the mediastinum in 37 cases (22%), in a deep cervical location in 34 cases (19%), or in an intrathyroidal location in 14 cases (8%), or were undescended in four cases (2%); supernumerary glands were found in 26 cases (15%). Some patients had more than one remaining abnormal gland. Selective venous catheterization with a parathyroid hormone assay was done in cases in which the results of noninvasive localization studies were equivocal or negative, and it frequently converted an equivocal result of a localization study to a definitely positive result. There were no complications from the localization studies. At reoperation, permanent hypoparathyroidism that required parathyroid autotransplantation of cryopreserved tissue developed in two patients and two patients had recurrent laryngeal nerve palsies. CONCLUSION: We currently recommend using ultrasonography and technetium Tc99m sestamibi scanning and magnetic resonance imaging for patients with recurrent or persistent HPT. Selective venous catheterization with a parathyroid hormone assay is done selectively. Localization tests decrease morbidity and improve overall results in these patients.

Adult↗
PubMed1994

Factors influencing the amplitude and frequency of essential tremor.

Quantitative electromyography (EMG) and triaxial accelerometry were used to measure hand tremor, finger tremor, and forearm motor unit activity in 36 men and 23 women with essential tremor. Hand tremor was studied with and without 300-g mass loading. Tremor and EMG were recorded twice, with a 3-min rest interval, to assess the spontaneous intertrial variability in tremor amplitude, frequency, and motor unit entrainment. In general, the minimum detectable differences in tremor amplitude, frequency, and motor unit entrainment were roughly 30%, 5%, and 10% of the initial sample means, respectively, assuming a sample size of 30 patients, a statistical power of 0.9, and a significance level of 0.05. Linear regression analyses were performed to test the hypotheses that (a) there is an age-associated decrease in tremor frequency that is independent of symptom duration and (b) tremor frequency and motor unit entrainment make independent contributions to tremor amplitude. Our data supported both hypotheses.

Adolescent↗
PubMed1994

Essential tremor entrains rapid voluntary movements.

The effect of essential tremor on the timing of rapid wrist flexion was examined in 10 patients with moderate to severe disability. The mean reaction time and motor time of the patients did not differ from the mean values of 10 healthy age- and sex-matched controls. The latencies of the triphasic agonist and antagonist EMG bursts did not differ between patients and controls. The initiation of movement was time-locked to the tremor cycle in all patients. The initial agonist muscle activation occurred in phase with the rhythmic bursts of EMG, but the onset of rapid wrist flexion occurred when the momentum of essential tremor opposed the volitional movement. Essential tremor has subtle effects on motor control that transcend oscillation per se. These effects probably contribute to the impaired performance of fine motor tasks in patients with advanced disease.

Aged↗
PubMed1994

Mutations in the rod 1A domain of keratins 1 and 10 in bullous congenital ichthyosiform erythroderma (BCIE).

Bullous congenital ichthyosiform erythroderma is a human hereditary skin disorder in which suprabasal keratinocytes rupture. Recent reports have implicated keratins K1 and K10 in this disease. Here we describe four diverse keratin mutations that are all significantly associated with this disease. Two of these are in the helix 1A subdomain of the type II keratin 1, giving a serine-to-proline substitution in codon 185 and an asparagine-to-serine substitution in codon 187. In the analogous region of type I keratin 10, an arginine-to-proline and an arginine-to-serine transition in codon 156 have been identified. All four mutations create restriction fragment length polymorphisms that were used exclude the mutations from 120 normal chromosomes. Insertional polymorphism (in the V2 subdomains of the non-helical tails of K1 and K10) was excluded as the cause of the phenotypic heterogeneity observed within one family.

Amino Acid Sequence↗
PubMed1994

Ichthyosis bullosa of Siemens--a disease involving keratin 2e.

Ichthyosis bullosa of Siemens (IBS) is a congenital bullous ichthyosis without erythroderma. In contrast to bullous congenital ichthyosiform erythroderma (BCIE), there is a relatively mild involvement of the skin and epidermolytic hyperkeratosis (EHK) is restricted to the upper suprabasal layers of the epidermis. Tonofilament aggregation was observed by EM in suprabasal cells from affected patients in the two families under study, indicative of a keratin abnormality. Keratin 2e is a differentiation specific type II keratin expressed suprabasally in the epidermis. Part of the K2e gene was amplified by polymerase chain reaction using genomic DNA from affected and unaffected individuals from two IBS families. Direct sequencing of polymerase chain reaction products revealed a point mutation in the highly conserved helix termination motif, producing the protein sequence change LLEGEE-LLEGKE. This mutation was found in all affected members of a five-generation kindred and also in a sporadic case in a second unrelated family. No mutation was seen in unaffected individuals. The mutation destroys a MnlI restriction site, which allowed exclusion of the mutation from a population of 50 unaffected unrelated individuals by restriction fragment analysis of K2e PCR products. This is the sixth keratin gene found to be involved in an inherited epidermal disorder.

Base Sequence↗
PubMed1994

The effect of the orally active platelet-activating factor antagonist WEB 2086 in the treatment of asthma.

Platelet-activating factor (PAF) may be a major mediator of asthma and bronchial hyperreactivity through its many proinflammatory actions. Specific antagonism of PAF might offer an alternative anti-inflammatory treatment to inhaled corticosteroids. To test this, we have studied the effect of an orally active PAF antagonist, WEB 2086, on the inhaled steroid requirements of symptomatic atopic asthmatics in a double-blind randomized placebo-controlled parallel group study. The inhaled corticosteroid dose required for symptomatic control of asthma was established and further steroid reduction was attempted after treatment with WEB 2086 40 mg three times daily for 12 wk. Of 106 patients recruited, 68 entered the treatment phase and 65 completed 6 wk of treatment. The mean daily corticosteroid dose (SE) at study entry was 1,257 (75) micrograms which was reduced by 323 (66) micrograms during the run-in period without loss of symptomatic control. A further 416 (57) micrograms reduction in inhaled corticosteroid dosage was possible during the treatment phase but this was almost identical in the WEB 2086 and placebo-treated groups, amounting to 353 (92) and 481 (65) micrograms/day respectively (not significant [NS]). Rate of relapse following corticosteroid reduction was a continuous variable and relapse occurred at different times depending on the variable used to define it. Time to relapse measured by an increase in symptoms correlated with disease duration (r = 0.41, p < 0.01) and with the dose of inhaled corticosteroid at study entry (r = 0.36, p < 0.01) but no other measured variable predicted the time to relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

Combined analysis of mortality in three United Kingdom nuclear industry workforces, 1946-1988.

Mortality during 1946-1988 has been analyzed in 75,006 employees of the United Kingdom Atomic Energy Authority, the Atomic Weapons Establishment and the Sellafield plant of British Nuclear Fuels. All-cause mortality was 19% lower than national rates among workers monitored for external radiation exposure and 18% lower among nonmonitored workers. Cancer mortality was also lower than national rates and was similar in the two groups of workers [rate ratio (RR) = 0.96]. Of 29 specific cancer sites examined, only for cancers of the pleura and uterus were there statistically significant excesses of mortality in monitored workers relative to nonmonitored workers [RR = 7.08, two-sided P (2P) = 0.008 and RR = 3.02, 2P = 0.003, respectively]. There was little association between cumulative external radiation and risk of death from all cancers combined 10 or more years after exposure [z for trend = +0.11, one-sided P (1P) = 0.5]. A positive association was observed for leukemia (assuming a 2-year lag between external radiation and increasing risk of death) (1P = 0.009) but not for other cancers associated with external radiation in previous analyses (lung, uterus, prostate and multiple myeloma, all 1P > or = 0.1). Positive associations (1P < or = 0.05) were also observed for melanoma and other skin cancers (1P = 0.03) and ill-defined and secondary cancers (1P = 0.04), but these results are difficult to interpret and, given the number of associations examined, may be chance findings. Estimates of excess relative risk per sievert were -0.02 (95% CI = -0.5-+0.6) for all cancers except leukemia and +4.18 for leukemia (95% CI = +0.4-+13.4). The positive estimates for leukemia contrast with negative values found for workers in the United States, although the confidence intervals obtained in the two studies overlap. While our estimates of risk are compatible with those derived from studies of A-bomb survivors, the statistical uncertainty associated with them is such that the data are consistent with risks ranging from no additional risk to twice the risk for cancers other than leukemia and, for leukemia, from one-fifth to three times the risk in A-bomb survivors.

Cause of Death↗
PubMed1993

Cancer mortality and morbidity in employees of the United Kingdom Atomic Energy Authority, 1946-86.

In further analyses of a cohort of 39,718 United Kingdom Atomic Energy Authority employees after 7 more years follow-up, cancer mortality, based on 1,506 deaths in 1946-86, was 20% below the national average. Prostatic cancer mortality showed a statistically significant association with external radiation exposure, largely confined to men who were also monitored for internal contamination by radionuclides other than plutonium. Prostatic cancer mortality was highest in radiation workers at Winfrith. In women monitored for radiation exposure, mortality from cancer of the uterus (including the cervix uteri) was increased relative to other employees, and, showed a statistically significant association with external radiation exposure. While there were some other statistically significant results, as would be expected by chance alone when multiple comparisons are made, there were no other cancer sites with consistently exceptional findings. Point estimates for risk associated with increasing exposure to radiation suggest a decrease of four deaths per 10(4) person-years per Sv for leukaemia and an increase of 20 deaths for all cancers except leukaemia, but confidence intervals indicate that a wide range of values are compatible with the data. Cancer morbidity based on 1,699 registrations in 1971-84 was 12% below the national average. Findings from site-specific analyses largely replicated those of the mortality analyses.

Cause of Death↗
PubMed1992

The syndrome of senile gait.

Infrared computed stroboscopic photometry was used to quantify the kinematic profiles of walking in 10 elderly patients with symmetrical neurological disturbances of gait and in 19 age-matched neurologically healthy people. Clinical examination of the patients revealed similar profiles of walking even though their diagnoses were vascular dementia (2), normal pressure hydrocephalus (2), Alzheimer dementia with possible normal pressure hydrocephalus (2), mixed Alzheimer and vascular dementia (1), peripheral neuropathy (1), Alzheimer dementia with parkinsonian features (1), and undetermined (1). Quantitatively, the patients' gait kinematics deviated greatly from control values, but these deviations were statistically attributable to reductions in stride. We suggest that many gait disturbances in elderly people are similar, regardless of etiology, because the characteristics of these gait disturbances are heavily veiled by nonspecific stride-dependent changes that comprise the syndrome of senile gait.

Aged↗
PubMed1992

Phase resetting and frequency entrainment of essential tremor.

Step and sinusoidal forcings were delivered to the wrists of 10 patients with advanced essential tremor using a computer-controlled torque motor. Consistent (type 0) phase resetting was produced in only 5 patients, whereas all 10 patients exhibited harmonic and 2:1 subharmonic entrainment of essential tremor. These results indicate that the oscillator of essential tremor is coupled to the stretch-reflex arc. Irregularity in the tremor rhythm and postperturbation mechanical-reflex oscillations obscured the phase of essential tremor, thereby impeding the computation of phase resetting curves. Sinusoidal forcings circumvented these problems, but frequency entrainment was produced only by forcings at frequencies within +/- 1 Hz of the tremor frequency and its second harmonic. Resonance accompanied frequency entrainment and probably plays a role in the clinical expression of tremor.

Adult↗
PubMed1992

Longitudinal study of essential tremor.

We measured wrist tremor and forearm EMG in 18 patients with essential tremor on two occasions separated by periods of 4 to 8 years. The frequency of tremor decreased 0.28 Hz to 3.21 Hz in 10 patients and changed less than 0.25 Hz in the remaining eight patients. Thus, the frequency of essential tremor may decrease over time.

Adult↗
PubMed1991

Stride-dependent changes in gait of older people.

Infrared computerized stroboscopic photometry was used to measure the kinematic profile of walking of 20 young adults and 20 neurologically healthy elderly people. Compared with the young adults, the elderly exhibited 17-20% reductions in the velocity of gait and length of stride. The elderly also exhibited comparable reductions in the maximum toe-floor clearance, arm swing, and rotations of the hips and knees, but these alterations in gait were attributable to the reduction in stride length, which may have non-neurological causes. The influence of reduced gait velocity and stride length on the other characteristics of walking must be considered when evaluating the pattern of walking in elderly people.

Adult↗