Permeability of human brain tumor to 99mTc-gluco-heptonate and 99mTc-albumin. Implications for monoclonal antibody therapy

The variable penetration of chemotherapeutic drugs into brain and tumor is more dependent upon lipid solubility than upon size. In contrast, the molecular weight of virus- and tumor-specific monoclonal antibodies appears to limit uptake. The authors have studied eight patients with malignant brain tumors in order to compare tumor uptake of an iodinated contrast agent evaluated by computerized tomography scanning with uptake of the low and high molecular weight imaging agents technetium-99m (99mTc)-glucoheptonate and 99mTc-albumin, respectively, measured by radionuclide brain scanning. The agent 99mTc-labeled albumin was chosen for evaluation because its molecular weight (68,000) is similar to that of the most clinically promising monoclonal antibody fragment, the immunoglobulin (Ig) G Fab monomeric fragment. The radionuclide brain scans in the eight patients showed highly variable permeability of brain tumor to these markers, with uptake of the high molecular weight marker in the tumor being much less than that of the low molecular weight radionuclide. A clinical implication of these studies is that the success of monoclonal antibody therapy in the treatment of malignant brain tumors may require techniques to increase permeability of the blood-brain barrier and blood-tumor barrier to protein.     

Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.     

Laparoscopically assisted hysterectomy.

OBJECTIVE: To determine the feasibility and effectiveness of laparoscopically assisted hysterectomy. DESIGN: A prospective study of the planned surgical procedure was carried out by two teams, each with two gynaecologists, who were experienced in operative laparoscopy. SETTING: The operations were carried out in a private hospital, where advanced operative laparoscopy equipment was available. PATIENTS: Seventeen patients were selected for the procedure, all of whom required hysterectomy for symptoms of pain or menorrhagia in association with uterine or other pelvic disease. Patients with carcinoma or uterine enlargement beyond 12 cm were excluded. PROCEDURE: Laparoscopically assisted hysterectomy was carried out by means of a video monitor, uterine manipulation by vaginal instrumentation, three or four abdominal punctures of less than 1 cm, and bipolar diathermy to secure vascular pedicles. The uterus was removed from the vagina by cutting vaginal skin and the cardinal ligaments. RESULTS: The operating time was 90-220 min, the blood loss was 30-200 mL, and the hospital stay lasted two to five days and convalescence two to four weeks. No serious complications occurred. CONCLUSIONS: Laparoscopically assisted hysterectomy may be valuable when adnexal or uterine abnormalities are present and vaginal hysterectomy is either contraindicated or more difficult. The procedure requires special equipment and may only be carried out by experienced gynaecological operative laparoscopists. Its acceptance will depend upon reducing the operating time to less than 90 min. It has the advantage of reducing the duration of hospital stay and the duration of convalescence when compared with abdominal hysterectomy.     

Use of the 90Sr applicator for intraoperative radiation therapy in a mouse tumor model

Intraoperative radiation therapy (IORT) research is limited by the lack of small-animal models. We have implanted B16 melanoma into mouse kidneys, which we subsequently operated upon and irradiated with beta rays from a ⁹⁰Sr ophthalmic applicator. The IORT has effectively prolonged survival and produced some cures. The strategy should be applicable to other murine tumors and to other internal implantation sites.     

Wound healing response in surgical patients: recent food intake is more important than nutritional status

We have recently found that an impairment of the wound healing response (WHR) occurs in surgical patients with protein-energy malnutrition before there are any measurable changes in body fat and protein stores. The hypothesis of this study was that the patients' recent food intake is more important in determining the WHR than the patients' overall nutritional status. We have measured the recent food intake (by dietary recall), the WHR (by hydroxyproline accumulation in subcutaneous GORE-TEX implants), the pre-operative weight loss (per cent), and body fat and protein stores (by in vivo neutron activation analysis) in 83 patients awaiting a major elective gastrointestinal resection, and divided them into two groups: adequate recent food intake (n = 59) and inadequate recent food intake (n = 24). There was no significant difference between these two groups for age, sex, diagnosis, surgical procedure, weight loss (per cent), or the amount of body fat and protein stores but there was a significant difference in the WHR (1.81 +/- 0.16 s.e.m. versus 1.04 +/- 0.22 s.e.m. nmol hydroxyproline/mg GORE-TEX, P less than 0.005). These results show that pre-operative food intake has a greater influence over the wound healing response than absolute losses of protein and fat from body stores and they suggest that the maintenance of a normal food intake up until the time of surgery is of importance in preventing an impairment of the wound healing response.     

A review of photoradiation therapy in the management of central nervous system tumours

Photoradiation therapy depends on the selective retention of a photosensitizer within the tumour followed by activation of the sensitizer by irradiating the tumour with light of the appropriate wavelength. The present methods of treatment of cerebral glioma are inadequate and the possible benefit of utilizing photoradiation therapy to obtain improved local control of the tumour has been studied in the laboratory and in clinical trials. The biological basis for photoradiation therapy and the laboratory studies and clinical trials involving the use of photoradiation therapy to treat cerebral tumours are discussed.     

Event-related Potentials as Markers for Alcoholism Risk in High Density Families

One hundred sixty-eight adult siblings and parents from affected and control families were tested for ERP characteristics using two tasks involving an auditory oddball paradigm. Significant within family differences among affected families suggest that risk for developing alcoholism may be seen even in adult subjects who have had experience consuming alcohol. Further, analysis of quantity and recency of drinking in the past seven days were not correlated with either amplitude or latency of P300, suggesting that the within-family differences observed reflect relative risk for developing alcoholism rather than experience with alcohol.     

Postural changes in perfusion pressure and retinal arteriolar calibre.

Ophthalmic artery perfusion pressures and retinal arteriolar calibres were studied in 10 human subjects when sitting, standing, and lying. Differing responses in perfusion pressure were found; autoregulatory responses were found in 13 of the 18 significant calibre changes on moving from sitting to standing and 13 of 22 significant calibre changes on moving from standing to lying. The remaining significant calibre changes were non-autoregulatory, the arterioles dilating with perfusion pressure increase and constricting with decrease.