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Biomedical subjects

N T Matthews

Publications and source records attributed to N T Matthews.

14 recordsLinked to original sources

Infant pertussis deaths in New South Wales 1996-1997.

Since 1996, south-eastern Australia has been experiencing a pertussis epidemic which has resulted in the deaths of several infants, including four from NSW in the 12 months to July 1997. All were less than six weeks of age and died from overwhelming cardiovascular compromise despite intensive care support. This excessive infant mortality from a preventable disease demonstrates the need for better pertussis immunity in the community and for erythromycin treatment of all suspected cases and family contacts, especially infants.

Disease Outbreaks↗

Relative bioavailability and plasma paracetamol profiles of Panadol suppositories in children.

OBJECTIVE: To determine the relative bioavailability and plasma paracetamol concentration profiles following administration of a proprietary formulation of paracetamol suppositories to postoperative children. METHODOLOGY AND RESULTS: Study A-eight children undergoing minor surgery had blood samples collected following the rectal administration of either a 250 mg or 500 mg paracetamol suppository on one day and an equivalent oral dose on the following day. A mean dose of 13 mg/kg gave a mean Cmax (Tmax) of 7.7 mg/L (1.6 h) and 4.9 mg/L (2.0 h) following oral and rectal administration, respectively. The mean relative rectal bioavailability was 78% (95% confidence interval of 55-101%). Study B-20 children undergoing tonsillectomy and/or adenoidectomy were randomly assigned to receive a postoperative dose of 500 mg of paracetamol either as 2 x 250 mg liquid filled or 1 x 500 mg hard wax Panadol suppository. A mean dose of 25 mg/kg produced mean maximum plasma paracetamol concentrations of 13.2 mg/L and 14.5 mg/L at 2.1 and 1.9 h for the hard and liquid filled suppository, respectively. The absorption rate constants and areas under the curves suggested no difference in the rate or extent of absorption between the two formulations. CONCLUSION: Absorption of paracetamol following rectal administration of Panadol suppositories to postoperative children is slower and reduced as compared to oral therapy. The hard wax and liquid filled products have similar absorption characteristics. The usually quoted antipyretic therapeutic range for paracetamol is 10-20 mg/L, although 5 mg/L may be effective. A single rectal dose of 25 mg/kg will obtain this lower concentration within 1 h of administration and maintain it for up to 6 h. When given in an appropriate dose for analgesia, maximum plasma paracetamol concentrations would be available in the immediate postoperative period if the rectal dose was given 2 h before the planned end of the procedure.

Acetaminophen↗

Phospholipase C-gamma 1 can induce DNA synthesis by a mechanism independent of its lipase activity.

Inositol phospholipid-specific phospholipase C (PLC) is involved in several signaling pathways leading to cellular growth and differentiation. Our previous studies reported the induction of DNA synthesis in quiescent NIH 3T3 cells after microinjection of PLC and the inhibition of serum- or Ras-stimulated DNA synthesis by a mixture of monoclonal antibodies to PLC-gamma 1. In the course of our investigation of anti-PLC-gamma 1 monoclonal antibodies, we found that each antibody exerts different inhibitory effects on the phosphatidylinositol-hydrolyzing activity of PLC-gamma 1 and that the inhibition of enzymatic activity does not correlate with the inhibition of DNA synthesis observed in the microinjection assay. PLC-gamma 1 with defective enzymatic activity was synthesized by substituting phenylalanine for histidine within the PLC-gamma 1 catalytic domain at amino acids 335 and 380, and mutant enzymes were expressed using a vaccinia expression system. The mutant enzymes were purified and microinjected into quiescent NIH 3T3 cells to evaluate their mitogenic activity. A moderate induction of DNA synthesis occurred after injection of mutant PLC-gamma 1. This mitogenic activity was inhibited by an antibody (alpha E 8-4) that does not significantly inhibit PLC-gamma 1 enzyme activity, which indicates that something else has to be inhibited. Furthermore, the partial induction of DNA synthesis observed with mutant PLC-gamma 1 was increased to levels seen with wild-type PLC-gamma 1 by coinjection of mutant PLC-gamma 1 with two second messengers, diacylglycerol and inositol trisphosphate. These results suggest that the mitogenic activity of PLC-gamma 1 does not exclusively result from the enzymatic activity of the lipase and that another activity inherent to the PLC-gamma 1 molecule can also induce DNA synthesis in quiescent cells.

3T3 Cells↗

Biological actions of oncogenes.

Cancer, in many cases, results from multistep genetic mutation. Certain genes can have a predisposed susceptibility to mutations that lead to cancer because of chromosome location or their importance in the control of cell cycles. Mutations that deregulate the expression or activity of enzymes involved in the biochemical pathways of growth and differentiation or that suppress the expression of negative cell cycle control factors result in activation of oncogenesis. The study of oncogenes and tumor suppressor genes has greatly influenced our understanding of the molecular origins of cancer. We focus here on the normal biological action of proto-oncogenes compared with the transforming activities of oncogenes and tumor suppressor genes, and we discuss possible mechanisms of oncogenic transformation.

Animals↗

Severe meningococcal septicaemia associated with splenic rupture.

OBJECTIVE: To present the first report of ruptured spleen associated with meningococcal septicaemia. CLINICAL FEATURES: A 13-year-old girl presented with an acute abdomen and clinical signs of meningococcal septicaemia. Features of her illness placed her in a high mortality group. INTERVENTION AND OUTCOME: She required cardiovascular and respiratory support in the Intensive Care Unit. Failure to initially identify the organism led to percutaneous fine-needle aspiration of fluid in the lesser sac. A laparotomy revealed free intraperitoneal blood and a ruptured spleen. During the course of her illness she was given penicillin and methylprednisolone, and required haemodialysis. She made a complete recovery. CONCLUSION: Ruptured spleen does occur with severe meningococcaemia, and may complicate management.

Adolescent↗

False negative HIV serology in a case of congenital/perinatal AIDS.

A case of congenital or perinatal Acquired Immunodeficiency Syndrome (AIDS), the first recognized case of mother to child human immunodeficiency virus (HIV) infection resulting in the full-blown syndrome in Australia, is reported. The baby who died in November 1985 was diagnosed retrospectively after the child's father had presented with Category A disease (Pneumocystis carinii pneumonia) in May 1987. This case illustrates some of the difficulties that may be experienced in the serological diagnosis of HIV in young children and foreshadows the effects of spread of HIV in the heterosexual community.

Acquired Immunodeficiency Syndrome↗

Ergotism with therapeutic doses of ergotamine tartrate.

Two cases of acute ergotism are described in patients taking therapeutic oral doses of ergotamine tartrate and concomitant triacetyloleandomycin. Both showed satisfactory response to infusion of sodium nitroprusside with normal perfusion being obtained in the affected limbs. The treatment of ergotism with sodium nitroprusside is reviewed and the apparent interaction of ergotamine and triacetyloleandomycin is discussed.

Adult↗

Mobile intensive care services in rural South Australia.

In the 12 years from 1984 to 1995, Adelaide-based mobile intensive care teams transported 4443 critically ill patients from rural areas in South Australia and adjacent States to tertiary-level hospitals in Adelaide. The SA Ambulance Service undertook communications, support staffing and deployment of transport. Average radial distances in 819 road missions were 71 km, in 808 helicopter missions 122 km, and in 2777 fixed-wing aircraft missions 398 km. The largest groups of patients were neonates (23%) and those with trauma (25%). Rural hospitals made 96% of the requests for intensive care transport; 4% came from ambulance or other emergency service crews at accident locations. Emergency surgical or operative obstetrical procedures were performed on 2.7% of patients before transport. One hundred and thirteen patients (2.5%) died during resuscitation or transport, with one death deemed to be preventable.

Ambulances↗