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Biomedical subjects

J Holt

Publications and source records attributed to J Holt.

At least 19 recordsLinked to original sources
PubMed1992

Casemix classification and Australian doctors. Risks and opportunities.

"Casemix" is an information tool--a set of patient care classifications and ideas about their use. It is useful only if it promotes understanding, and leads to better performance of the health system. Here we discuss some uses of casemix classifications, including payment of hospitals on a per case basis. Clinicians need to be concerned about both the design of casemix classifications themselves, and the ways in which they are used.

Australia↗
PubMed1992

Estrogen and progesterone withdrawal increases cerebral vasoreactivity to serotonin in rabbit basilar artery.

An in vitro animal model which examines the effects of sex hormone variations during the menstrual cycle on basilar artery reactivity is presented. Three groups of rabbits were utilized: a chronically depleted control group which received no further hormonal treatment after bilateral surgical oophorectomy (O), simulating menopause, and two groups of intact females, one of which was treated to mimic the estrogen and progesterone surge during the luteal phase (H) and the third group which was acutely estrogen and progesterone depleted after the luteal surges to simulate the immediate premenstrual state (W). We show that both acute and chronic estrogen and progesterone withdrawal significantly increase serotonin sensitivity (ED50) in basilar artery rings. There was no difference between groups for maximum contraction (Tmax) to serotonin, nor optimal resting tension. Furthermore, there was no difference in vasoreactivity and contractility to norepinephrine between groups. In order to distinguish between the effects of chronic and acute treatment we examined acute estrogen and progesterone superfusion in basilar artery rings from intact non-treated female rabbits. Acute superfusion of pre-contracted and non-pre-contracted artery segments resulted in significant dilatation only when supraphysiologic concentrations of estrogen and progesterone were used. We conclude that both acute and chronic female sex hormone withdrawal selectively increases cerebral vasoreactivity to serotonin.

Animals↗
PubMed1992

The effects of established diabetes on the growth of the fetal liver and skin in the rat.

1. The effects of uncontrolled maternal diabetes on the growth of the whole rat fetus and its liver and skin were studied over the last 4 days of gestation. 2. Smaller fetuses, with growth-retarded livers and skins, were consistently found between 18 and 21 days in the diabetic pregnancies. 3. The smaller diabetic livers and skins (i.e. combined epidermis and dermis) possessed lower protein, RNA and DNA contents, compared with the same fetal tissues from normal pregnancies. 4. The growth retardation of the livers in diabetic fetuses was attributed to fewer normally sized hepatic cells. 5. Whilst hepatic rates of protein synthesis (measured in vivo) remained largely unchanged, these were actually increased in the skin, compared with normal control tissues. 6. These findings point to an elevated rate of protein degradation in both diabetic tissues as the most likely cause of their retarded growth.

Animals↗
PubMed1992

Production and functional characterization of a recombinant fragment of von Willebrand factor (vWF): an antagonist to platelet receptor GP Ib.

We expressed a recombinant peptide fragment (Ser445-Val733) of human von Willebrand factor (vWF), containing the binding domain for the platelet receptor of GP Ib, in E. coli. This 33 kD peptide blocks binding of the intact vWF molecule to GP Ib in the presence of modulators. Thus, it offers potential as an antithrombotic agent. High level expression was achieved in a plasmid construct driven by the bacteriophage T7 promoter. The peptide was solubilized from inclusion bodies in strong chaotrope, then reduced and alkylated. Following purification, formulation at pH 3.5, and lyophilization, the reconstituted experimental product (RG 12986) exists as an equilibrium of monomer and dimer species. When formulated above pH 5.0, soluble aggregates are formed; these solutions have less bioactivity than RG 12986. Interestingly, the non-aggregated state of RG 12986 remains conserved following dilution and incubation with platelet-poor plasma. The overall purification/low pH formulation strategies may be applicable to other E. coli recombinant proteins having a tendency to aggregate following removal of chaotrope near physiologic pH when in a concentrated format.

Cloning, Molecular↗
PubMed1991

Growth of the rat foetal liver in gestational diabetes.

1. Through a combination of streptozotocin and insulin injections an animal model of gestational diabetes has been established, whereby blood glucose concentrations are elevated over the second-half of pregnancy. 2. Between 18 and 21 days of gestation the diabetic mothers carried smaller foetuses, which in turn possessed growth retarded livers. 3. This suppression of hepatic growth in diabetic foetuses was evident in terms of consistently decreased (7-27%) liver weights and protein and nucleic acid contents. 4. No differences were found between the rates of hepatic protein synthesis (measured in vivo) in control and diabetic foetuses. 5. Hence, the growth retardation of the foetal liver, arising from maternal hyperglycaemia, must necessarily involve an increase in protein degradation.

Animals↗
PubMed1991

Initial experience with a practical hyperfractionated accelerated radiotherapy regimen.

This paper presents early results of a trial of a three-fractions-per-day (TID) regimen that is more convenient to schedule than the Continuous Hyperfractionated Accelerated Radiotherapy (CHART) protocol currently being tested in Europe. The treatment schedule used in the CHART regimen has been modified from 36 fractions of 1.5 Gy TID in 12 days to 72 fractions of 1.1 Gy in 24 treatment days, with all fractions delivered during normal working hours. With no weekend treatments, the entire course of radiotherapy is completed in less than 5 weeks. The doses used were determined using the L-Q model, with correction for incomplete repair between fractions and for accelerated repopulation of cancer cells. Comparison with historical controls shows statistically significant improvements both in CR rates for the primary tumor and in acute toxicity, as measured by reduced treatment interruptions. L-Q model calculations predict that, compared to the highest dose achieved in previous studies without exceeding tolerance, we are able to obtain a 12% increase in bioeffect dose to the primary tumor due to accelerating the treatment. An analysis of the potential tumoricidal effectiveness of this new treatment regimen shows that it should be better than several other accelerated fractionation schedules being tested for all values of Tpot. For short Tpot times, the advantage may be as much as one log cell kill, corresponding to a 10-15% potential improvement in local control.

Aged↗
PubMed1990

Elegantin and albolabrin purified peptides from viper venoms: homologies with the RGDS domain of fibrinogen and von Willebrand factor.

The RGD-containing peptides isolated from the venoms of the Viperidae constitute a new class of small cysteine-rich peptides of variable amino acid composition and biological activity (Huang, T.-F., et al. (1987) J. Biol. Chem. 262, 16157-16163; Gan, Z.R., et al. (1988) J. Biol. Chem 263, 19827-19832; Huang, T.-F., et al. (1989) Biochemistry 28, 661-668), which it is proposed by Gould et al. (unpublished data) that we call 'disintegrins'. These peptides bind to the glycoprotein IIb-IIIa receptor on the platelet surface and inhibit aggregation induced by ADP, thrombin, platelet-activating factor and collagen. These peptides are also potent inhibitors of cell adhesion to fibrinogen (Knudsen, K.M., et al. (1988) Exp. Cell Res. 179, 42-49). We report the isolation of two further RGD-peptides from the venoms of Trimeserusus elegans and Trimeserusus albolabris, purified to homogeneity with high yield by a novel, rapid reverse-phase HPLC method. The primary structures of these two peptides were determined to be single polypeptide chains of 73 amino acids. Albolabrin differed from trigramin by eight residues whilst elegantin differed by 22 residues. The molecular mass of albolabrin calculated on the basis of amino acid sequence was 7574 Da and the pI similarly calculated was 4.27. The molecular mass of elegantin was calculated to be 7806 Da and the theoretical pI to be 4.69. RGD is maintained in the same position (51-53 AA) and all 12 cysteines are identical. Our data suggest that the presence of RGD, the conserved secondary and tertiary structure, are essential for the expression of biological activity by these peptides. Both peptides inhibited ADP-induced platelet aggregation. Extended homologies around the RGDS sequences in human von Willebrand Factor and bovine fibrinogen were found with both peptides.

Amino Acid Sequence↗
PubMed1990

A regular pattern of two types of 100-residue motif in the sequence of titin.

Titin is the largest polypeptide yet described (relative molecular mass approximately 3 x 10(6); refs 1, 2) and an abundant protein of striated muscle. Its molecules are string-like and in vivo span from the M to Z-lines. I-band regions of titin are thought to make elastic connections between the thick filament and the Z-line, thereby forming a third type of sarcomere filament. These would centre the A-band in the sarcomere and provide structural continuity in relaxed myofibrils. The A-band region of titin seems to be bound to the thick filament, where it has been proposed to act as a 'molecular ruler' regulating filament length and assembly. Here, we show that partial titin complementary DNAs encode a regular pattern of two types of 100-residue motif, each of which probably folds into a separate domain type. Such motifs are present in several evolutionarily divergent muscle proteins, all of which are likely to interact with myosin. One or both of the domain types is therefore likely to bind to myosin.

Amino Acid Sequence↗
PubMed1989

Immunoregulatory activity of peptides related to platelet factor 4.

Platelet factor 4 (PF4), a secreted platelet protein, alleviates concanavalin A-induced immunosuppression in mice. We now find that activity also resides in (i) the C-terminal tridecapeptide of PF4 (P13S), (ii) an analog of this in which arginine replaces the lysine residues and in which the last two amino acids are absent, (iii) the C-terminal 18 amino acids of low-affinity platelet factor 4, which is very similar to P13S, and (iv) peptide fragments of P13S that contain only 5-9 amino acids. P13S treated with fluorescamine to derivatize the free amino groups retained immunoregulatory activity but did not bind to heparin-agarose. The N-terminal and middle portions of PF4, polylysine, protamine, and three unrelated peptides were inactive in this assay.

Amino Acid Sequence↗
PubMed1979

Prospective study of chlamydial infection in neonates.

Chlamydia trachomatis was recovered from the cervices of 4% (36/900) of pregnant women tested. 20 infants born through chlamydia-infected cervices were followed up for a year, as were 18 infants born to chlamydia-negative mothers. A statistically significant excess of conjunctivitis and pneumonia was found in infants exposed to chlamydia. The attack-rate for inclusion conjunctivitis was 35% (7/20) and for chlamydial pneumonia it was 20% (4/20). Chlamydiae were recovered from 10 of the 20 (50%) exposed infants, and seroconversion was demonstrated in 14 (70%). None of the 18 unexposed infants showed evidence of chlamydial infection. Thus in our clinic 2.8% of all newborns acquired chlamydial infection, with incidence-rates of 14 cases of conjunctivitis and 8 cases of pneumonia per 1000 live births. Neonatal chlamydial infection is thus a major public-health problem warranting a preventive programme based on the fuller provision of diagnostic services and the treatment of infected pregnant women.

Cervix Uteri↗
PubMed1979

Infection with Chlamydia trachomatis: involvement of multiple anatomic sites in neonates.

In a study of infection due to Chlamydia trachomatis in infants, chlamydiae were recovered not only from the conjunctiva and respiratory tract but also from the vagina and rectum. The timing of recovery suggested that the vagina and conjunctivae are exposed to chlamydiae at birth and that pneumonia and gastrointestinal infection occur later. Sampling of the rectum may be a useful procedure for the diagnosis of chlamydial disease in infants.

Chlamydia Infections↗
PubMed1979

Mortality and complications of large-bowel resection for carcinoma.

The mortality and complications of large-bowel resection for carcinoma performed at the Princess Alexandra Hospital since the Colorectal Project commenced in 1971 are reviewed and compared with the results in other published series. There were 443 patients in this prospective study, and 375 underwent resection of their tumour. The overall operative mortality was 6.4% - for colonic lesions it was 8.0% and for rectal 3.4%. The mortality for elective curative resections was 2.6%, and for emergency resections it was 10.8%. The anastomotic leak rate was 6.8%, but was higher (16.6%) when the anastomosis was done at the time of emergency resection. No patient whose anastomosis leaked but who had had a previous defunctioning proximal colostomy died. There was a wound infection rate of 15.1%.

Adult↗
PubMed1978

The effects of drought on human nutrition in an Ethiopian province.

In mid 1974 the authors conducted a survey of Harerghe Province, Ethiopia in order to verify reports of serious effects of drought six months earlier. Information was obtained on anthropometric nutritional status, mortality, livestock, and market prices from a random sample of 62 villages in four ecological zones - the highlands, the northern and southern rangelands and an intermediate zone of mixed economy. The rangelands and intermediate areas had experienced heavy human and livestock losses during the drought but this had not occurred in the highlands. Although a high prevalence of malnutrition was found in every area studied, the geographical and height distribution of malnutrition within population groups suggested that this could only be clearly attributed to the effects of unusual food shortage in one part of the southern rangelands.

Adolescent↗