Social aspects in the changing epidemiology of malaria in the highlands of New Guinea.

The increase in movement of people both within the highlands of New Guinea and also to and fro between holo- and hyperendemic lowland areas and the highlands by policemen and semi-skilled personnel in one direction and by labourers in the other, together with a great increase in potential breeding sites, were virtually inevitable consequences of the development process as the intense communalism and geographical isolation of the highland people was broken down. Prior to the "opening up" of the highlands, evidence suggests that malaria had existed in an endemic and very unstable form in only a few lower altitude areas and in the populations of the perimeter villages who had contact with lowland areas. This paper traces the changes in the distribution and determinants of malaria that occurred pari passu with the development process in the highlands of Papua New Guinea between 1930 and 1970.     

The profile of patients referred to an outreach restorative dentistry clinic over the last 10 years has changed

The aim of the study was to compare the profile of the patients referred to a Restorative Dentistry consultant clinic at Scarborough General Hospital (SGH) in 1991 and 2001. The clinical records from 80% of a cohort of the new patients referred for consultation and who attended in 1991 and 2001 were examined. In total 55 clinical records were examined from 1991 and 84 from 2001. Data on reason for referral, time of wait before assessment and outcome of the consultation was recorded. The number of patients seen for consultation increased considerably between 1991 and 2001. Mean waiting times from the date of referral to the date when assessed trebled (p = 0.016). Referral for denture problems (notably complete dentures) was the main reason for referral in 2001 (25%). Tooth wear was the most common reason for referral in 1991 (22%). It was concluded that the demand for the services of a Restorative Dentistry consultant at Scarborough General Hospital increased considerably between 1991 and 2001. This resulted in considerably longer waiting times for a consultation. In 2001 there was a greater percentage of referrals for appearance, complete dentures and implants. A higher percentage of patients in this study were referred back to their GDP for treatment as compared to other studies.     

Effects of intraventricular injections of norepinephrine on brain-pituitary-ovarian function in the rabbit

In estrous estrogen-primed female rabbits with electrodes chronically implanted in various subcortical regions of the brain, the intraventricular injection of an ovulation-inducing dose of norepinephrine (NE) stimulated a prolonged episode of high amplitude 40-60 cps electroencephalographic (EEG) activity in the olfactory bulb (OB) and its projections. This activity, which started usually between 30 and 60 min after NE injection and was maintained continously for periods up to an hour thereafter, was regularly absent in the same rabbits when they were pseudopregnant and non-ovulatory to NE. Similar OB-EEG activity and ovulation had been observed earlier in response to intraventricular histamine under light pentobarbital anesthesia. The ovulatory response to histamine was eliminated by massive midbrain lesions or removal of the olfactory bulb, but intraventricular NE still induced ovulation after such losses. The ovulatory effectiveness of NE was blocked, however, by low doses of pentobarbital or high doses of atropine, neither of which inhibited the ovulatory response to intraventricular epinephrine. Atropine and alpha-adrenergic blocking agents also prevented the ovulatory response to intraventricular histamine. It is suggested that histamine activates pituitary-ovarian function by stimulating central noradrenergic elements and that NE has more of the physiological-pharmacological characteristics of a natural central nervous activator of luteinizing hormone-releasing hormone than has epinephrine.     

Autotransplantation of ovarian tissue and the risk of disease transmission

Temporary ovarian function has been reported following reimplantation of frozen/thawed cortical tissue and it is hoped that in time this technique will allow women sterilised by treatment for cancer to regain their fertility. There is however a concern, supported by animal data, that ovarian tissue may be contaminated by disease capable of causing a relapse after transplantation. One experiment, in which ovarian tissue from women with lymphoma was xenografted into immunodeficient mice, showed no evidence of transmission but these results require confirmation and no data exists for other malignancies. For the time being, therefore, it is recommended that harvesting and reimplantation of ovarian tissue should only take place within the confines of carefully designed clinical trials.     

A UK multi-centre pilot study of speech and swallowing outcomes following head and neck cancer

Speech and swallowing are important components of health-related quality of life following head and neck cancer treatment. The aim of this study was to demonstrate the value of prospective multi-centre evaluation by Speech and Language Therapists and to compare health-related quality of life with speech and swallowing impairments. The University of Washington Head and Neck questionnaire version 4 (UW-QOL) and Therapy Outcome Measures (TOM) were rated before and 6 months after cancer treatment in 95 patients from 12 centres. There was deterioration in TOM scores at 6 months. Pretreatment UW-QOL swallowing was ranked equal first, with speech fourth. At 6 months speech was first and swallowing second. There were positive correlations between UW-QOL swallowing and TOM dysphagia and between UW-QOL speech and TOM laryngectomy, voice, phonology and dysarthria disorders. Both outcome measures are suitable for routine practice. Adaptation of TOM scales for use with head and neck cancer patients may improve sensitivity, validity and therapist compliance.     

Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: presentation of MART1 to CD8+ T cells

The generation of tumour-specific cytotoxic T-lymphocyte (CTL) responses is the primary focus in the design of immunotherapeutic cancer vaccines. We have recently demonstrated generation of ovalbumin (OVA)-specific CTLs and tumour-protection in a murine tumour model using vaccination with dendritic cells (DCs) pulsed with E. coli expressing listeriolysin O (LLO) and OVA as a model antigen. In this system paraformaldehyde fixation of E. coli/LLO provided an additional safety feature without compromising vaccine efficacy. We therefore reasoned that paraformaldehyde-fixed recombinant E. coli expressing LLO would be an efficient vehicle for the delivery of human tumour antigens to human DCs. In the present study, we demonstrate that fixed E. coli expressing LLO are taken up efficiently by human monocyte-derived DCs (MoDCs) with minimal toxicity. As a consequence of the interaction with bacteria, human DCs undergo marked phenotypic and functional maturation. Furthermore, we show that fixed E. coli/LLO expressing the well-characterised human melanoma antigen, MART1, efficiently deliver the HLA-A2-restricted MART1(27-35) epitope for processing and presentation on human MoDCs, suggesting the potential of this system as a novel strategy for human tumour immunotherapy.     

Isolation of germ cells from human testicular tissue for low temperature storage and autotransplantation

OBJECTIVE: To develop a new protocol for conserving fertile potential in men undergoing sterilizing chemotherapy by low temperature banking of germ cells which can be returned to the patient's testes after thawing. DESIGN: Isolation of human and murine germ cells for comparing cellular viability after cooling to liquid nitrogen temperatures by the use of different cryoprotective agents and for infusion into the testis. SETTING: Laboratory research environment. PATIENT(S): Men undergoing routine surgery in a urology department. INTERVENTION(S): Testicular biopsy. MAIN OUTCOME MEASURE(S): Cellular viability and infusion of seminiferous tubules. RESULT(S): After isolation using a two-step enzymatic disaggregation protocol, 66% to 87% of germ cells from human and murine specimens, respectively, were still viable. Cell survival was similar in four commonly used cryoprotective agents after cooling to liquid nitrogen temperatures. Seminiferous tubules infused by back flow with dye solution via the rete testis were filled with an efficiency of 55%. CONCLUSION(S): Judging from the high viability of unfractionated germ cells, it is feasible to isolate germ cells from testicular biopsies for low temperature banking with the aim of attempting to restore fertility after iatrogenic sterilization.