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Biomedical subjects

G Cruickshank

Publications and source records attributed to G Cruickshank.

15 recordsLinked to original sources
PubMed2000

Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma.

The herpes simplex virus (HSV) ICP34.5 null mutant 1716 replicates selectively in actively dividing cells and has been proposed as a potential treatment for cancer, particularly brain tumours. We present a clinical study to evaluate the safety of 1716 in patients with relapsed malignant glioma. Following intratumoural inoculation of doses up to 10(5) p.f.u., there was no induction of encephalitis, no adverse clinical symptoms, and no reactivation of latent HSV. Of nine patients treated, four are currently alive and well 14-24 months after 1716 administration. This study demonstrates the feasibility of using replication-competent HSV in human therapy.

Adult↗
PubMed2000

Audit of headache following resection of acoustic neuroma using three different techniques of suboccipital approach.

A retrospective case notes review using pain visual analogue scale (VAS) and assessment of analgesia required by patients in the post-operative period at 1, 3, 6, 12 and over 12 months following acoustic neuroma resection was performed. Glasgow Benefit Inventory (GBI) score was used to assess the change of quality of life and its relationship to pain following surgery. Questionnaires of 71 patients were included in the study, 23 of whom underwent wide craniotomy including dissection of upper cervical musculature (CE), 25 wide craniotomy with replacement of bone flap (CO) and 23 minimally invasive, approximately 2 x 2 cm, minicraniectomy (MCE). The minicraniectomy resulted in significantly diminished pain from third month post surgery as compared with wide craniectomy (p < 0.05) and patients required less analgesia. Similarly, CO patients have experienced significantly less pain than CE patients (p < 0.05), but only after 12 months following surgery. Although consistently less in absolute visual analogue scores, there was no statistically significant difference between the amount of pain recorded by CO and MCE patients. There was no correlation between gender or age and the VAS pain score. The mean Glasgow Benefit Inventory score for all patients was -6.6, and there was no significant difference between operation types, genders or age. Although bone flap replacement appears to diminish the amount of post-operative pain, minimal invasive technique resulted in least pain following acoustic neuroma resection in our patients.

Female↗
PubMed1996

Selective in vitro replication of herpes simplex virus type 1 (HSV-1) ICP34.5 null mutants in primary human CNS tumours--evaluation of a potentially effective clinical therapy.

Primary tumours of the central nervous system (CNS) are an important cause of cancer-related deaths in adults and children. CNS tumours are mostly glial cell in origin and are predominantly astrocytomas. Conventional therapy of high-grade gliomas includes maximal resection followed by radiation treatment. The addition of adjuvant chemotherapy provides little improvement in survival time and hence assessment of novel therapies is imperative. We have evaluated the potential therapeutic use of the herpes simplex virus (HSV) mutant 1716 in the treatment of primary brain tumours. The mutant is deleted in the RL1 gene and fails to produce the virulence factor ICP34.5. 1716 replication was analysed in both established human glioma cell lines and in primary cell cultures derived from human tumour biopsy material. In the majority of cultures, virus replication occurred and consequential cell death resulted. In the minority of tumour cell lines which are non-permissive for mutant replication, premature shut-off of host cell protein synthesis was induced in response to lack of expression of ICP34.5. Hence RL1-negative mutants have the distinct advantage of providing a double hit phenomenon whereby cell death could occur by either pathway. Moreover, 1716, by virtue of its ability to replicate selectively within a tumour cell, has the potential to deliver a 'suicide' gene product to the required site immediately. It is our opinion that HSV which fails to express ICP34.5 could provide an effective tumour therapy.

Animals↗
PubMed1994

Direct measurement of pO2 distribution and bioreductive enzymes in human malignant brain tumors.

PURPOSE: To measure the oxygen status of human malignant brain tumors in vivo and to determine the activities and expression of bioreductive enzymes in these same human brain tumor samples, as a means of assessing their suitability as targets for bioreductive drug therapy. METHODS AND MATERIALS: A polarographic oxygen electrode was used to measure the intratumoral oxygen tension in twenty patients with malignant brain tumors during open brain surgery, performed under standard anaesthetic conditions. Six different tracks, each with a path length of 22 mm, were recorded per patient representing 192 readings. Following pO2 measurements the tumors were resected and stored in liquid N2 for subsequent bioreductive enzyme analysis. Eight human malignant brain tumors were assessed, by enzyme activity and western blot expression, for the presence of various bioreductive enzymes. These enzymes included DT-diaphorase, NADH cytochrome b5 reductase, and NADPH cytochrome P-450 reductase. Of these eight gliomas analyzed six samples were incubated with the bioreductive drug tirapazamine, in the presence of cofactor(s), to establish whether human brain tumors could metabolize this compound. RESULTS: Both the high grade intrinsic and metastatic brain tumors showed significant regions of hypoxia. All the tumors subjected to enzyme profiling contained the bioreductive enzymes, DT-diaphorase, NADH cytochrome b5 reductase and NADPH cytochrome P-450 reductase. Also all six of the brain tumors investigated could metabolize tirapazamine to the two-electron reduction product. CONCLUSION: These findings would favor primary brain tumors as suitable targets for bioreductive therapy.

Brain Neoplasms↗
PubMed1993

Acute perforated duodenal ulcer is not associated with Helicobacter pylori infection.

Most patients with chronic duodenal ulcer disease have Helicobacter pylori infection and eradicating it considerably reduces the relapse rate. The prevalence of H pylori in 80 patients (mean age = 52 years, range 17-85) presenting with acute perforated duodenal ulcer was examined and compared with age and sex matched hospital control patients. H pylori state was assessed by serum anti-H pylori IgG (Helico-G kit, Porton) using a titre of 18 or less as negative with a specificity of 89% and sensitivity of 88%. Only 47% of the perforated duodenal ulcer patients were positive for H pylori and this was similar to the value of 50% in the controls. In 51 of the perforated duodenal ulcer patients 14C-urea breath tests were also performed 4-10 weeks after surgery and this confirmed that only 49% were positive for H pylori. None of these patients had received perioperative drugs that might have eradicated the infection. The H pylori positive and H pylori negative perforated duodenal ulcer patients were similar with respect to age (53, 51), smoking (84%, 83%), and consumption of more than 15 units of alcohol per week (42%, 38%). Duodenal ulcer disease had been diagnosed before acute perforation in only 24% of those with H pylori and also 24% of those without the infection. Regular non-steroidal anti-inflammatory drug (NSAID) use was common in both those with (44%) and without (45%) H pylori. In conclusion, the lack of association of acute perforated duodenal ulcer and H pylori infection suggests that perforated duodenal ulcer has a different pathogenesis from chronic duodenal ulcer disease, and that the first should not be regarded simply as a complication of the second.

Acute Disease↗
PubMed1993

Measurement of serum arabinitol by gas-liquid chromatography: limitations for detection of systemic candida infections.

The measurement of serum arabinitol in the diagnosis of systemic candidosis was evaluated using a gas-liquid chromatography technique in a cohort of at risk patients. The prevalence of seropositivity was low and did not correlate with evidence of infection. This technique is unlikely to achieve acceptance because it does not discriminate between patients with and without infection; it requires specialised equipment and it is expensive.

Candidiasis↗
PubMed1977

Rhinocerebral mucormycosis.

Rhinocerebral mucormycosis is a fungal diseases that has a 50% mortality. Its occurrence has increased, possibly because of greater use of chemotherapeutic agents that mya compromise the immunologic defenses of the host or alter the normal flora. The earliest signs, ulceration and pain, may appear in the mouth. In the patient described in this report, the autopsy showed that mucormycosis had entered the brain cells.

Amphotericin B↗