Pasteurization of milk: the heat inactivation kinetics of milk-borne dairy pathogens under commercial-type conditions of turbulent flow.

This is the first study to report kinetic data on the survival of a range of significant milk-borne pathogens under commercial-type pasteurization conditions. The most heat-resistant strain of each of the milk-borne pathogens Staphylococcus aureus, Yersinia enterocolitica, pathogenic Escherichia coli, Cronobacter sakazakii (formerly known as Enterobacter sakazakii), Listeria monocytogenes, and Salmonella was selected to obtain the worst-case scenario in heat inactivation trials using a pilot-plant-scale pasteurizer. Initially, approximately 30 of each species were screened using a submerged coil unit. Then, UHT milk was inoculated with the most heat-resistant pathogens at ~10(7)/mL and heat treated in a pilot-plant-scale pasteurizer under commercial-type conditions of turbulent flow for 15s over a temperature range from 56 to 66°C and at 72°C. Survivors were enumerated on nonselective media chosen for the highest efficiency of plating of heat-damaged bacteria of each of the chosen strains. The mean log(10) reductions and temperatures of inactivation of the 6 pathogens during a 15-s treatment were Staph. aureus >6.7 at 66.5°C, Y. enterocolitica >6.8 at 62.5°C, pathogenic E. coli >6.8 at 65°C, C. sakazakii >6.7 at 67.5°C, L. monocytogenes >6.9 at 65.5°C, and Salmonella ser. Typhimurium >6.9 at 61.5°C. The kinetic data from these experiments will be used by the New Zealand Ministry of Agriculture and Forestry to populate the quantitative risk assessment model being developed to investigate the risks to New Zealand consumers from pasteurized, compared with nonpasteurized, milk and milk products.

Intra-tumour genetic heterogeneity and poor chemoradiotherapy response in cervical cancer.

BACKGROUND: Intra-tumour genetic heterogeneity has been reported in both leukaemias and solid tumours and is implicated in the development of drug resistance in CML and AML. The role of genetic heterogeneity in drug response in solid tumours is unknown. METHODS: To investigate intra-tumour genetic heterogeneity and chemoradiation response in advanced cervical cancer, we analysed 10 cases treated on the CTCR-CE01 clinical study. Core biopsies for molecular profiling were taken from four quadrants of the cervix pre-treatment, and weeks 2 and 5 of treatment. Biopsies were scored for cellularity and profiled using Agilent 180k human whole genome CGH arrays. We compared genomic profiles from 69 cores from 10 patients to test for genetic heterogeneity and treatment effects at weeks 0, 2 and 5 of treatment. RESULTS: Three patients had two or more distinct genetic subpopulations pre-treatment. Subpopulations within each tumour showed differential responses to chemoradiotherapy. In two cases, there was selection for a single intrinsically resistant subpopulation that persisted at detectable levels after 5 weeks of chemoradiotherapy. Phylogenetic analysis reconstructed the order in which genomic rearrangements occurred in the carcinogenesis of these tumours and confirmed gain of 3q and loss of 11q as early events in cervical cancer progression. CONCLUSION: Selection effects from chemoradiotherapy cause dynamic changes in genetic subpopulations in advanced cervical cancers, which may explain disease persistence and subsequent relapse. Significant genetic heterogeneity in advanced cervical cancers may therefore be predictive of poor outcome.

Laparoscopic assisted vaginal hysterectomy and bilateral salpingo-oophorectomy as a day surgery procedure: a promising option.

Laparoscopic surgical techniques are increasingly being used to treat gynaecological malignancies as studies confirm long-term results similar to open procedures. Within the UK National Health Service, there is a drive towards day of surgery admission and reducing inpatient stay. We audited the length of inpatient stay, acceptability to patients of day of surgery admission and timing of discharge and accessibility to early community follow-up, among women undergoing laparoscopic assisted vaginal hysterectomy and bilateral salpingo-oophorectomy in our unit over a 6-month period. We show that women find short inpatient stays acceptable and that many can be safely discharged, with no postoperative hospital follow-up, within 24 h. Adequate pre-admission procedures and easy access to advice, post-discharge must be ensured.

Spinal cord compression and blood flow. I. The effect of raised cerebrospinal fluid pressure on spinal cord blood flow.

The effect of cerebrospinal fluid pressure (CSFP) on spinal cord blood flow (SCBF), measured by the hydrogen clearance technique, was studied in dogs. CSFP was altered by the infusion of mock CSF into the lumbar subarachnoid space. Occluding snares at T-13 limited the effect of raised pressure on the brain. As the perfusion pressure was reduced when the CSFP was increased, flow remained constant up to a perfusion pressure of approximately 50 mm Hg. Below this value, flow decreased with decreasing perfusion pressure. Normal flow values could be reestablished even at a raised CSFP if the perfusion pressure was increased by raising the arterial blood pressure. Rapid reduction of CSFP was accompanied by reactive hyperemia. The autoregulation of flow down to a perfusion pressure of 50 mm Hg was due to progressive decrease in vascular resistance. Carbon dioxide-responsiveness of the vessels was decreased markedly as the perfusion pressure was reduced.

The prognostic significance of beta human chorionic gonadotrophin and its metabolites in women with cervical carcinoma.

AIMS: To examine long term survival of women with primary and recurrent cervical carcinoma in relation to (1) excretion of beta-core (a urinary metabolite of beta human chorionic gonadotrophin (beta hCG)) and (2) beta hCG immunostaining of the tumours, to determine the suitability of these markers for assessing prognosis. METHODS: This was a prospective observational study undertaken in a gynaecological oncology centre: 57 women with primary cervical cancer and 42 with recurrent disease were recruited between January 1990 and September 1992. Kaplan-Meier survival analysis with the log rank test was used to assess survival differences with survival rate given per year of follow up. RESULTS: In primary disease, the four year survival for the beta-core negative group was 79%, compared with 14% for the beta-core positive group (p = 0.001). This was still significant for early stage disease or squamous lesions alone. In recurrent disease, beta-core positivity was not prognostically significant. Immunohistochemistry was of no prognostic significance in either group. CONCLUSIONS: beta-core excretion appears to be useful in assessing prognosis of primary cervical cancer but not of recurrent disease. A large prospective study of urinary beta-core in early stage cervical cancer is needed to determine whether it can be used as an index for modifying treatment.

Spinal cord blood flow measured by a hydrogen clearance technique.

Spinal cord blood flow (SCBF) has been measured in segments of the thoracolumbar cord of dogs using the hydrogen clearance technique. Clearances were recorded and flows calculated from electrodes placed in grey and white matter. The position of the recording electrodes was marked by diathermy and confirmed in each experiment. The SCBF in the white matter for 82 clearances was 13.7+/-4.5 ml/100 g/min using pentobarbitone anaesthesia. In the grey matter both monoexponential and biexponential clearances were recorded from electrodes placed in grey matter. There was no difference in flows calculated from the monoexponentail and slow components. SCBF from the slow components or monoexponentials was 12.0+/-4.5 ml/100g/min. The flow from the fast component was 69+/-11 ml/100 g/min. with pentobarbitone anaesthesia and 97.5+/-32.9 ml/100g/min with alpha-chloralopse anaesthesia. The flow calculated from the fast component did not correlate to changes of PaCO2. The slow component of any biexponential clearances was used to calculate flows from electrodes placed in the grey matter. There was no significant difference between flows from the grey matter (calculated from the slow component) and the white matter. Simultaneously recorded cortical and sub-cortical -lows were higher than in spinal grey and white matter. There was considerable variation in flow from animal to animal. The area of spinal grey matter is small and surrounded by white matter and the flow recorded from electrodes placed in grey matter is probably the average SCBF representing a mixture of grey and white flow. This will arise because of the rapid diffusibility of hydrogen gas between the tissues. It is therefore difficult to ascribe the flow from a centrally placed cord electrode to a definite anatomical compartment.

Immunization against Nippostrongylus brasiliensis in the rat. A study on the use of antigen extracted from adult parasites and the parameters which influence the level of protection.

It was found that protective immunity in excess of 90% reduction in worm burden could be stimulated against Nippostrongylus brasiliensis in rats by using an extract of adult Nippostrongylus worms. The level of protection achieved was influenced by several factors. Thus, the use of Bordetella pertussis as adjuvant significantly increased the level of protection which, in addition, was shown to be influenced by the amount of worm antigen used. Furthermore, antigen administered in multiple doses was more effective than a single inoculum and, when using such a regime, the interval between doses was also found to be critical. The route of antigen administration was important and, while protection was achieved by subcutaneous and oral administration, the intraperitoneal route was the most effective. Using the optimal immunization regime of 3 doses of 5 mg worm protein and 4 x 10(10( B. pertussis organisms, as adjuvant, levels of protective immunity in excess of 90% reduction in worm burden were shown to exist for at least 60 days after the last dose. It was found that adult worm extracts did not stimulate any obvious immunity against larval forms of N. brasiliensis.

The effect of norepinephrine on the spinal cord circulation and its possible implications in the pathogenesis of acute spinal trauma.

The effect of intra-arterially administered norepinephrine (NE) upon spinal cord blood flow (SCBF), before and after disruption of the blood-cord barrier was studied in dogs. Barrier disruption was accomplished with an intra-arterial bolus injection of 2.5 M urea. Multiple ligations of branches of the posterior aorta and cannula placements ensured that the urea was directed to the lumbar and sacral segments of the cord. The SCBF was measured by the hydrogen clearance method. Intra-arterial urea by itself had no significant effect on SCBF. The intra-arterial infusion of NE (12 microgram/min and 30 microgram/min) was without overall effect on SCBF. However, if the blood-cord barrier had been previously disrupted with hypertonic urea, both concentrations of NE resulted in large reductions in SCBF. No such reductions in SCBF were seen with blood-cord barrier disruption and NE if the animals had been pre-treated with the alpha-blocker, phenoxybenzamine (1.5 mg/kg). Some aspects of the possible involvement of NE in the pathophysiology of acute spinal injury are discussed.

Spinal cord blood flow and conduction during experimental cord compression in normotensive and hypotensive dogs.

Spinal cord blood flow (SCBF) and dorsal column conduction, as assessed by the dorsal column evoked potential (DCEP), were measured during subacute cord compression in dogs. Ventral, midline balloons were used to produce compression and a dorsally situated strain gauge transducer measured the cord pressure. In normotensive animals there was autoregulation of SCBF to perfusion pressures (PP) of 65 to 70 mm Hg, and up to cord pressures of 55 to 60 mm Hg. The DCEP amplitude was significantly decreased even during this autoregulatory period. Conduction failure occurred at PP of 20 to 30 mm Hg. Chemically produced hypotension (74 mm Hg) did not affect either SCBF or DCEP. Minimal compression superimposed on hypotension decreased both flow and DCEP amplitude. The results indicate that ischemia is probably not the cause of the impaired conduction although, as the degree of compression increases, the cord will become ischemic once the autoregulatory limit is passed.

The response of feline spinal pial arterioles to norepinephrine.

The effect of norepinephrine on the diameter of feline spinal pial arteries and arterioles was studied by microapplication of the drug to the perivascular environment. Vascular diameter was determined by the television image-splitting method. Application of norepinephrine over the range of 5 x 10(-8) M to 5 x 10(-3) M to spinal pial arterioles resulted in constriction of the vessels. The dose-response curve showed a tendency to plateau at concentrations above 5 x 10(-5) M, with a maximal constriction of 28.8 +/- 5.1% at 5 x 10(-3) M. The reduction in vessel diameter to microapplication of norepinephrine was prevented with the inclusion of an equimolar concentration of the alpha-adrenergic blocker, phentolamine, in the injectate. The data indicate the presence of alpha-adrenergic receptors on the smooth muscle of spinal pial arterioles, and it is suggested that the arguments pertaining to the sympathetic control of blood flow in the brain apply also to the spinal cord.

Risk of malignancy index in the preoperative evaluation of pelvic masses.

OBJECTIVES: To assess the ability of a risk malignancy index (RMI) based on serum levels of CA 125, ultrasound findings, and menopausal status to discriminate between benign and malignant pelvic masses in a particular population. METHODS: A retrospective study was conducted of 100 women with pelvic masses admitted for laparotomy. The sensitivity and specificity of serum levels of CA 125, ultrasound findings, and menopausal status were calculated both separately and combined into a RMI to diagnose malignancy. RESULTS: The RMI was more accurate than any single criterion in diagnosing malignancy. Using a cut-off level of 200 to indicate malignancy, the RMI gave a sensitivity of 90%, specificity of 89%, positive predictive value of 96%, and negative predictive value of 78%. CONCLUSION: The RMI is able to correctly discriminate between malignant and benign pelvic masses. It is a simple scoring system that can be introduced easily into clinical practice to facilitate the selection of patients who would benefit from primary surgery.

Barriers to effective communication across the primary/secondary interface: examples from the ovarian cancer patient journey (a qualitative study).

Effective communication across the primary/secondary interface is vital for the planning and delivery of appropriate patient care throughout the cancer patient journey. This study describes GPs' views of the communication issues across the primary/secondary interface in relation to ovarian cancer patients using qualitative interviews with purposively sampled general practitioners (GPs) and an audit of hospital medical records of 30 deceased ovarian cancer patients. Issues raised by the GPs related to the content and format of communications, but of most concern was the tardiness. The time lag between dictation and typing letters ranged from 0 to 27 days, with a delay of up to 8 days for signing before transit through various mail systems to the GP. Three stages in the patient journey were characterized by particular issues: (1) in the pre-diagnostic and diagnostic stage was a need for prompt information regarding the results of tests and diagnoses, and clearer guidance on the use of tests and fast-track referrals; (2) in the active treatment phase, when GPs could lose touch with their patients, they needed effective communication in order to provide moral support and crisis management; and (3) when oncology withdrew and the focus of care switched back to the community for the terminal phase, GPs needed information to enable them to pick up the baton of care. There is a need to develop and evaluate interventions aimed at improving the content and speed of communications between secondary and primary care. Such interventions are likely to be complex and might include the greater use of telephone or fax for more selected communications, a review of secretarial support, the use of email, the development of GP designed proformas, the feasibility of patient/carer letter delivery options, nurse-led communication, universal electronic patient records, or a revisiting of the patient-held record.

Reconstructive procedures in benign and malignant gynecological surgery.

The management of female cancers may involve radical surgery and radiotherapy, which results in damage to or loss of the pelvic organs and female genitalia. New procedures have been developed and applied in gynecological oncology, allowing reconstruction of continent bladders, of new vaginas (both for cosmesis and function), and preserving fecal continence. The use of a range of plastic procedures have enabled the restoration of the external appearances, which leads to improved recovery and a better quality of life.

Ovarian cancers related to minimal access surgery.

OBJECTIVE: To review the clinical features of women with ovarian cancer on whom minimal access surgery has been performed and to determine guidelines for the safe use of minimal access surgery for adnexal masses. DESIGN: Postal survey of members of the British Gynaecological Cancer Society (BGCS) and retrospective case review. RESULTS: BGCS consultants used ultrasound scanning (70%) and serum CA-125 estimations (53%) prior to adnexal mass surgery. The membership felt that adnexal masses with solid elements, diameter greater than 8 cm, multi-ocular or bilateral cysts or increased blood flow on Doppler scanning should not be operated on by minimal access surgery. A positive family history was also considered to be a contraindication. A total of 29 cases of ovarian cancer were identified on whom MAS had been performed. The incidence of cases was 4.1% of referrals to a tertiary referral centre (the Royal Marsden Hospital). The median age of patients was 37 years (range 20 to 68 years) and 13 had State I cancers. The mean delay between diagnosis and staging was 6.5 weeks. CONCLUSION: Guidelines on the use of minimal access surgery in the management of adnexal masses need to be agreed. Women who have an ovarian cancer diagnosed whilst having minimal access surgery should have an accepted staging procedure. We do not recommend the routine use of minimal access surgery for the treatment of ovarian cancer outside a trial.

Radical trachelectomy: a way to preserve fertility in the treatment of early cervical cancer.

In the Centenary year of Wertheim's hysterectomy for the treatment of invasive cervical cancer, it is appropriate to look at less radical methods of managing early stage disease. Radical trachelectomy with pelvic lymphadenectomy is a conservative but locally radical procedure, preserving the corpus uteri and therefore fertility potential. The first 10 cases in a pilot study are presented. One patient has required post-operative radiotherapy and another a completion radical hysterectomy. Three live births by caesarean section and three other pregnancies have resulted. Careful selection within strict criteria may allow this more conservative approach without compromising cure. These procedures should be carried out in referral centres with continuing follow up and review.

Elevated levels of insulin-like growth factor binding protein-1 in fetal distress.

OBJECTIVE: To investigate the association between fetal distress (abnormal cardiotocograph tracing and/or a low fetal pH) and the levels of fetal IGFBP-1. DESIGN: Prospective comparative study. SUBJECTS AND METHODS: Twenty-two women in labour with evidence of fetal distress defined by FIGO criteria and 19 women in uncomplicated labour. The gestation range was 37 to 42 weeks and birthweight range was 2500 to 4240 g. IGFBP-1 was determined by radioimmunoassay. RESULTS: The umbilical levels of IGFBP-1 were significantly higher in the study group compared with the control group (median 282.5 micrograms/l versus 128 micrograms/l, P = 0.0046; Mann-Whitney U test). There was a significant inverse correlation between fetal IGFBP-1 and cord pH (r = 0.58, P < or = 0.0001). There was no difference between the maternal serum levels of IGFBP-1 in the two groups. CONCLUSION: Umbilical IGFBP-1 is elevated in association with fetal distress.

Intrapartum amniotic fluid index and its relationship to fetal distress.

Amniotic fluid index was measured in 50 consecutive laboring women after membrane rupture. The 10th percentile of the normal range was 6.2 cm. Thirty-three women had a repeat measurement by a second observer. Although there was no systematic bias between the two observers, the limits of agreement were wide: 95% of the measurements by one observer were between 0.59 and 2.07 times those of the second. Closer agreement was observed when amniotic fluid index was low (less than 6.2 cm). The relationship between intrapartum amniotic fluid index and fetal distress was then investigated in a further 60 laboring women. When compared with women with a normal intrapartum amniotic fluid index, women with a low amniotic fluid index had higher incidences of fetal heart rate abnormalities during the first stage of labor (64% vs 20%, p less than 0.01), meconium (grade II or III) at delivery (64% vs 35%, p less than 0.05), and operative delivery for fetal distress (57% vs 17%, p less than 0.01). Umbilical artery pH and Apgar scores were, however, similar for the two groups. Measurement of intrapartum amniotic fluid index may be an appropriate method for selecting women suitable for intrapartum aminoinfusion.

The importance of serial biophysical assessment of fetal wellbeing in gastroschisis.

OBJECTIVE: To review antenatal and intrapartum assessment of pregnancies complicated by gastroschisis. DESIGN: Retrospective descriptive study. SETTING: University College Hospital, London. SUBJECTS: 24 consecutive cases of gastroschisis between 1986 and 1991. RESULTS: The gestational age at sonographic diagnosis was 20.3 weeks (SD 6.77) and at birth was 36.5 weeks (SD 2.06). There were 21 live births, all with good surgical outcome. There were 16 vaginal deliveries and eight caesarean sections. The elective sections were for oligohydramnios and dilated bowel (1) and clinically suspected growth retardation (1); the intrapartum caesarean sections were for fetal distress (4) and premature breech presentation (2). There were six with dilated gut on ultrasound; one of these ended in a stillbirth. There was a significant association between gut dilatation and caesarean section for fetal distress (P = 0.004). There was also a significant association between meconium staining and fetal distress (P = 0.021). Of these babies, 46% were < or = third centile for corrected birth weight. CONCLUSIONS: While half of the babies with gastroschisis were small for gestational age at birth, reliable antenatal prediction of birth weight is difficult. Gut dilatation may be an indicator of either antenatal or intrapartum fetal distress, but does not correlate with poor neonatal surgical outcome. We suggest close antenatal surveillance of fetal wellbeing in all cases of gastroschisis because, in addition to growth retardation, many show some evidence of fetal distress and 12.5% end in stillbirth, even when appropriately grown.