Biomedical subjects
M Gregory
Publications and source records attributed to M Gregory.
Fibroblast growth factor-2 (FGF-2) is present in maternal and cord serum, and in the mother is associated with a binding protein immunologically related to the FGF receptor-1.
Fibroblast growth factor-2 (FGF-2) is expressed in human fetal tissues and placenta. We, therefore, determined whether FGF-2 appeared in either fetal or maternal circulations during normal pregnancies [fetuses appropriate for gestational age (AGA)] or those complicated by fetal growth restriction (small for gestational age). Cordocentesis was performed, and matched maternal blood was collected between 19-39 weeks gestation, whereas maternal and cord blood and amniotic fluid (AF) were collected at term. FGF-2 was extracted from maternal serum (MS), cord serum (CS), and AF by heparin-Sepharose affinity chromatography and subjected to Western blot analysis or quantified by specific RIA. Western blot analysis of MS, CS, and AF revealed, in each case, a single immunoreactive FGF-2 species of 18 kilodaltons (kDa), although this was not present in nonpregnant serum. In AGA pregnancies, immunoreactive FGF-2 was present in MS from at least 18 weeks gestation and rose to maximum values at the end of second trimester (weeks 28-31; mean +/- SEM, 342 +/- 62 pmol/L), but by term had declined (weeks 40-42; 104 +/- 24 pmol/L). In CS, FGF-2 immunoreactivity was highest at weeks 18-20 of gestation (662 +/- 144 pmol/L), but thereafter, slowly declined to term (weeks 40-42; 119 +/- 28 pmol/L). Immunoreactive FGF-2 levels in MS and CS of small for gestational age pregnancies in the second trimester tended to be lower than those in AGA pregnancies, but differences were not statistically significant. AF also contained immunoreactive FGF-2 at term (91 +/- 35 pmol/L). Neutral gel chromatography on Sephadex G-200 revealed that FGF-2 immunoreactivity eluted as a broad peak with an apparent molecular size of 55-160 kDa. These same fractions contained peptides of 55-60, 90-95, and 120-130 kDa, which were recognized by antisera against the extracellular domain of the high affinity FGF receptor, FGFR1, after Western blot. Ligand blot analysis of the same nitrocellulose filters using 125I-labeled FGF-2 revealed that the 55- to 60-kDa species specifically bound FGF-2. This binding species was not recognized during Western blot analysis using an antiserum raised against the intracellular tyrosine kinase domain of FGFR1, suggesting that it represents a truncated receptor form. Similar FGFR1 immunoreactive species were present in nonpregnant female and male sera, but were barely detectable in term CS or AF.(ABSTRACT TRUNCATED AT 400 WORDS)
Fibroblast growth factor 2 is elevated in term maternal and cord serum and amniotic fluid in pregnancies complicated by diabetes: relationship to fetal and placental size.
We previously detected immunoreactive fibroblast growth factor 2 (FGF-2) in maternal and fetal circulations. Here, we determined whether the amounts of FGF-2 in term maternal serum, cord serum, and amniotic fluid were altered in pregnancies complicated by diabetes, as these are associated with a higher incidence of fetal macrosomia and increased placental size. Serum and amniotic fluid were collected at term from normal pregnancies (n = 17), women with pregestational insulin-dependent diabetes (n = 37; group A), patients with previously undiagnosed diabetes (n = 32; group B), women with gestational diabetes (n = 85; group C), and women with a milder form of glucose intolerance in pregnancy (n = 16; group D). Mean newborn weight and length, and placental weight did not significantly differ between normal and diabetic pregnancies, although the placental weight tended to be higher in the latter. However, 24% of the infants in group A and 19% in group B had a birth weight in excess of the 90th percentile. Levels of insulin in cord serum and amniotic fluid in groups A and B were significantly elevated compared to control values. FGF-2 was extracted from serum and amniotic fluid by heparin-Sepharose affinity chromatography and subjected to Western blot analysis or quantified by specific RIA. Western blot analysis of maternal serum, cord serum, and amniotic fluid from diabetic pregnant patients revealed, in each case, a single immunoreactive FGF-2 species of 18 kilodaltons; this was absent from nonpregnancy serum. In normal term pregnancies, the mean immunoreactive FGF-2 level in cord serum was 119 +/- 28 pmol/L, and that in amniotic fluid was 91 +/- 35 pmol/L. Values were significantly increased (2- to 4-fold) in both cord serum and amniotic fluid for all groups of diabetic patients. The mean FGF-2 level in normal term maternal serum was 104 +/- 24 pmol/L, and this was significantly increased in diabetic patients in groups B and C. The amount of FGF-2 in maternal serum showed a positive correlation with newborn weight and length, and placental weight (P < 0.05 or better, by Spearman rank correlation), and significant positive correlations also existed between the amounts of FGF-2 in cord serum and newborn or placental weight. The results suggest that the FGF-2 levels in maternal serum, cord serum, and amniotic fluid at term are elevated in pregnancies complicated by diabetes, and that the amounts of FGF-2 in maternal serum and cord serum are correlated with fetal and placental size.
Outcomes research in clinical practice. Descriptive studies are unhelpful.
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A study on the effects of low haemoglobin on postnatal women.
OBJECTIVE: to assess the effect of low haemoglobin (Hb) on the mental and physical health of postnatal women. DESIGN: survey conducted between May 1991 and February 1992. SETTING: maternity unit in district general hospital in the UK. PARTICIPANTS: 1010 postnatal women who had delivered a live baby, did not stay in hospital for seven or more days postnatally, whose baby was not admitted to the neonatal unit and who did not have a current psychiatric disorder. MEASUREMENTS: Hb levels at 'booking', 34 weeks gestation, three days and six weeks post delivery; the Edinburgh Postnatal Depression Scale (EPDS) and a self-completion questionnaire at ten days, four weeks and six weeks post delivery. FINDINGS: women with a low Hb are more likely to be under 25 years of age, primiparous, be anaemic at 34 weeks gestation, not to have had a normal delivery, have had a blood loss greater than 250 ml and to have had heavy lochia postnatally. Low Hb levels were not associated with high EPDS scores. Low Hb levels were related to reports of low energy, breathlessness, faintness/dizziness, painful perineal sutures and tingling in fingers and toes at ten days post delivery. Whilst tiredness persisted to six weeks post delivery the other symptoms disappeared. IMPLICATIONS FOR PRACTICE: in order to reduce the incidence of postnatal anaemia a review of policies for testing is recommended so that the incidence of physical problems in the first six weeks can be reduced. There is a need for further research into the causes and potential alleviation of tiredness.
Follow up of women with a history of mildly abnormal cervical smears which have returned to normal without treatment.
The progress of 124 women with at least two negative cervical smears following a history of mildly abnormal smears for which no treatment had been given was compared with 106 women with negative smears and a clinical history of genital warts or herpes virus infection and 460 age-matched controls. After 4 years, excluding those for whom there was no follow up, 5.8% of those with a history of abnormal smears, none of those with a clinical history of genital warts or herpes virus and 1.1% of controls had developed histological evidence of at least cervical intraepithelial neoplasia grade III (CINIII) when referred for investigation of subsequent abnormal smears; one woman, from the control group, had developed invasive cervical cancer. Women with two negative smears after a history of abnormal smears who subsequently developed CINIII were more likely to have had a previous smear reported as moderate or mild-moderate dyskaryosis (2/6) compared with those whose follow up was negative (2/89). The results suggest that two negative cervical smears may not necessarily indicate that a lesion has regressed, but that a clinical history of genital warts or herpes virus infection should not be an indication for increased surveillance.
Lesch-Nyhan syndrome and the lower lip guard.
Lesch-Nyhan syndrome, a rare inborn error of metabolism, is characterized by mental retardation and factitious oral lesions, which cause immense difficulties in its management. A case of an 11-year-old boy, the elder of two siblings with this condition, who had severe self-inflicted injuries to oral and perioral tissues is presented highlighting the different treatment modalities considered. A tailor-made lipguard proved to provide the best cosmetic result short term.
The clinical project coordinator.
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A clinical study of the Brånemark dental implant system.
A clinical study using the Brånemark dental implant system was carried out on 13 patients aged 41 to 68 years. Clinical and psychological effects of treatment were assessed at 6-monthly intervals over a period of 3 years by means of a clinical examination, a personality assessment using Cattell's 16 PF Questionnaire and a general subjective questionnaire. Six per cent of implants failed to osseointegrate. Fifty per cent of bridges became loose, but remained stable after retightening. A similar percentage of fractures occurred, mainly teeth separating from acrylic gumwork. There was some soreness of peri-implant mucosa, particularly on cleaning. Despite these problems, there was considerable evidence of improved well-being of patients, who felt more secure following treatment and, as a result, their personal and social relationships improved.
Response to nondepolarizing muscle relaxants in children with tumours.
The rate of onset of action of d-tubocurarine (64 patients) or alcuronium (36 patients) was studied electromyographically in 100 children who had abdominal, bone or cerebral tumours. It was found that there was a significantly delayed onset (over three times longer than controls) or additional doses were required in patients with malignant liver, renal and bone tumours who received d-tubocurarine. The onset of alcuronium blockade was also prolonged but to a lesser extent. When tumours with an abnormal prolongation of onset of relaxation were successfully treated by chemotherapy and/or surgery, the response reverted to normal. Children with benign tumours or masses had normal responses. In contrast, neuroblastomas were associated with little prolongation of onset. Cerebral tumours showed a variable response, with the observed changes being unreliable indicators of degree of malignancy.
Finite element analysis of fixed prostheses attached to osseointegrated implants.
The effect of defined stresses on cantilevered prostheses attached to osseointegrated implants was assessed by finite element analysis. The effect of stress on a cantilever, consisting of a ductile alloy in contact with a brittle polymer, was demonstrated to be complex. The distribution of applied stresses also influenced the results. Possible fracture and distortion of both materials were demonstrated. Finite element analysis is a particularly useful system for predicting stress behavior and can be employed to produce an optimal prosthetic design that reduces the potential for clinical failure.
Clonidine transdermal patches for use in outpatient opiate withdrawal.
We conducted a study to assess the clinical usefulness of transdermal clonidine for heroin detoxification in an outpatient drug treatment clinic. Twenty-two young otherwise healthy heroin addicts participated. Outcome was assessed on the basis of (a) hypotension and other side effects of clonidine; (b) patient retention; (c) concomitant drug use; (d) subjective symptoms of withdrawal; and (e) objective signs of withdrawal. Side effects were present but in no case necessitated discontinuation of treatment. Drop-out rates were equal to conventional treatment offered at the clinic. The availability of clonidine broadens the therapeutic options available to patients and clinicians in treating the opiate-addicted patient. Transdermal clonidine offers several advantages over the oral form: patches can be applied weekly, fewer supplemental medications are required, and patches supply an even blood level of medication. A protocol for use is recommended.
Insulin and renal sodium retention in obese adolescents.
The effect of insulin on the renal handling of sodium was studied in obese and nonobese subjects by using euglycemic hyperinsulinemia. Seven water-loaded obese (14-19 years old) and five nonobese young adults (18-21 years old) had insulin given intravenously at a rate of 40 munits/m2/min. Blood glucose and creatinine clearance were not altered by euglycemic hyperinsulinemia in either the obese or the nonobese group. Hyperinsulinemia resulted in a significant decrease in urinary sodium excretion in both groups of subjects (by 54.2 +/- 3% [mean +/- SEM] in the obese and by 50.9 +/- 3.1% in the nonobese group). However, the amount of glucose required to maintain euglycemia was significantly less in the obese versus nonobese group, 89.5 +/- 6.2 versus 329.2 +/- 16 mg glucose/m2/min (p less than 0.001). There was no relation in either group between the amount of glucose required to maintain euglycemia and the change in urinary sodium excretion. On a separate day, all of the obese subjects underwent 3 hours of water diuresis but without insulin. There was no change in urinary sodium excretion with sustained water diuresis alone. However, when compared with the nonobese group, the obese group of subjects had a significantly higher resting mean arterial pressure, heart rate, and plasma norepinephrine concentration; during the insulin clamp, neither group experienced a significant change in mean arterial pressure or heart rate, and only the nonobese group experienced an increase in plasma norepinephrine. In obese subjects, we have found, despite the presence of insulin resistance to carbohydrate metabolism, that euglycemic hyperinsulinemia was associated with a normal decrease in urinary sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Teaching lip-reading: the efficacy of lessons on video.
Studies of the efficacy of filmed and videotaped materials for lip-reading self instruction have provided encouraging results. The recent increase in private ownership of VCRs allows widespread home use of video lessons for improving lip-reading skills. Such an approach is particularly, useful for hearing-impaired adults who have no access to lip-reading classes. To fill this need in Australia a 3-hour video cassette of nine lip-reading lessons was produced. The video lessons were tested over a period of 5 weeks. The study showed a significant improvement in the lip-reading skill of students who studied the video cassette compared to a control group who did not. The extent of improvement did not differ for students who studied the video in a class, at home, or as supplementary teaching material. While the age and sex of the subjects did not influence improvement of lip-reading skills, the study showed greater improvement for the relatively poorer lip-readers. More detailed testing of one group of students showed generalization of lip-reading skills to unfamiliar speakers and materials.
BMX bicycle injuries in hemophiliacs.
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Properties of equine anti-lipopolysaccharide hyperimmune plasma: binding to lipopolysaccharide and bactericidal activity against gram-negative bacteria.
Anti-lipopolysaccharide equine hyperimmune plasma (anti-LPS), which has been used successfully to treat LPS (endotoxin)-mediated disorders, has been further characterised. IgG present in anti-LPS had the highest affinity for LPS prepared from Salmonella typhimurium, S. typhi, S. abortus equi and Shigella flexneri and intermediate affinity for Escherichia coli O55:B5, E. coli O127:B8 and S. enteritidis. Anti-LPS destroyed by means of complement activation a wide range of gram-negative bacteria, including various species and strains of Klebsiella, Enterobacter, E. coli, Sh. flexneri, Providencia, Salmonella and Pseudomonas. Control plasmas or saline had little or no effect. Maximum killing occurred within seconds to minutes. Electronmicroscopy showed that anti-LPS treatment of K. pneumoniae caused extensive cell wall and cytoplastic membrane disruption, followed by the appearance of spheroplasts and cell ghosts. Antibodies were required in 100,000-fold excess to inhibit the limulus amoebocyte lysate reaction with LPS from E. coli. Anti-LPS thus contains IgG that binds to a wide range of LPS, and can destroy a wide range of gram-negative bacteria by means of complement activation.
Liver tumours and muscle relaxants. Electromyographic studies in children.
Electromyographic studies of the onset of action of tubocurarine or alcuronium were performed on eight occasions in five patients who had liver masses. There was a slow onset of action and an increased dose requirement in those with malignant disease. Normal responses were found in a patient with benign nodular hyperplasia and in another where the malignant tumour was successfully treated with chemotherapy.
Pneumococcal carriage amongst Australian aborigines in Alice Springs, Northern Territory.
In Alice Springs and its vicinity, a single nasal swab was collected from 282 Australian aborigines in May 1981 to determine nasal carriage rates of pneumococci. Each swab was inoculated on blood agar and on gentamicin blood agar. The carriage rates were 89% in children, 39% in adolescents and 34% in adults. In all, 27 serotypes of pneumococci were met with and 15 (4%) of subjects yielded two or more serotypes. In children, types 23, 19, 6, 22 and 6 were predominant (in that order), whereas type 3 was commonest in older subjects. Approximately 25% children and 5% adults yielded drug-insensitive pneumococci. Resistance to benzylpenicillin, tetracycline and co-trimoxazole was met with, resistant pneumococci showed five resistance patterns and belonged to nine serotypes, predominantly types 19 and 23. All isolates were sensitive to chloramphenicol, erythromycin, lincomycin and rifampicin. The carriage rate of drug-insensitive pneumococci was 100-fold higher amongst children sampled than in non-aboriginal children in Australia.