Effects of Taxol plus radiation on the apoptotic and mitotic indices of mouse intestinal crypt cells.

PURPOSE: In this study we investigated the effect of Taxol, radiation, or Taxol plus radiation on highly proliferative normal tissue--the intestinal crypt cells of Swiss albino mice. MATERIALS AND METHODS: Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered by bolus intravenously through the tail vein. Radiation was given using a linear accelerator. There were four treatment categories, which comprised a total of 34 groups. Each group consisted of five animals. The first category was a control category which comprised one group (n = 5). The second treatment category was Taxol alone which comprised three groups (n = 15). The third treatment category was radiation alone which comprised three groups (n = 15). The fourth treatment category was Taxol plus radiation which comprised 27 groups (n = 135). Mice were killed 24 h after Taxol or radiation or combined administration using ether anesthesia. Using a light microscope, apoptotic and mitotic indices were counted on jejunal crypt cells of mice that were stained with hematoxylin-eosin. Differences between groups were statistically evaluated with Student's t-test. RESULTS: Taxol caused a dose-dependent increase in apoptosis (P = 0.045) and decreased the mitotic index (P = 0.006) at high doses. Similarly, radiation caused a dose-dependent increase in apoptosis (P = 0.046) and decreased the mitotic index (P = 0.299) at higher radiation doses. Compared to radiation alone, Taxol caused a significant induction of apoptosis (P = 0.010). In combination, no significant radiosensitizing effect of Taxol was observed (enhancement ratio < 1), when compared to radiation alone. However, an increase in apoptosis was observed after 24 h of Taxol exposure when compared to 12 or 48 h of Taxol exposure (P = 0.0001 and P = 0.0001). CONCLUSION: These findings suggest that Taxol did not cause a radiosensitizing effect in intestinal crypt cells. However, a 24-hour pretreatment of Taxol exposure followed by radiation caused significant induction of apoptosis and reduction of the mitotic index when compared to other Taxol timing sequences. Thus, the lack of a radiosensitizing effect of Taxol in these proliferative cells may be due to enhanced mitotic death rather than apoptotic death.

Unusual appearance of intracranial fibromuscular dysplasia. A case report.

Fibromuscular dysplasia (FMD) of intracranial arteries is seen rarely and usually limited to the intrapetrosal internal carotid artery or carotid siphon. The authors report a case with recurrent subarachnoid hemorrhage diagnosed angiographically as FMD with extensive involvement of intracranial arteries. Angiography showed large fusiform dilatations and multiple aneurysms along the left intracranial internal carotid artery into its major branches, middle cerebral and posterior communicating arteries, and tip of the basilar and posterior cerebral arteries. Such an angiographic appearance has not been previously reported. Radiologic findings are demonstrated and possible pathophysiologic mechanisms are discussed.

Giant schwannoma of the trigeminal nerve misdiagnosed as maxillary sinusitis. A case report.

A 24-year-old woman presented with left-sided ptosis, diplopia, sensory impairment on the left side of her face and diminished hearing in her left ear. The neurological findings were hypo-anesthesia in all three divisions of the trigeminal nerve, left-sided facial paralysis of the oculomotor and abducens nerves. Initially the condition was misdiagnosed as maxillary sinusitis and was treated with antibiotics. It seems that this presentation has not been previously described in commonly read English-language journals. In our case, the tumour was removed totally and the neuropathological diagnosis was schwannoma. The case report describes the presentation, investigations, management and outcome in this patient.

The outcome effect of double-hormonal therapy in premenopausal breast cancer patients with high nodal-status: Result of a prospective randomized trial.

PURPOSE: The combination of taxanes and anthracyclines has proven efficacy in node-positive (N+) premenopausal primary breast cancer patients. Ovarian ablation is also associated with better survival outcomes in premenopausal hormone-receptor positive (HR+) patients. Therefore, this trial aims to determine the superiority of combined hormonal treatment of ovarian ablation with tamoxifen (TMX) versus TMX alone, in premenopausal N+, HR + patients receiving adjuvant chemotherapy (AC) with taxane and anthracycline. MATERIALS AND METHODS: Premenopausal women who had surgically removed breast cancer with histologically confirmed N + and HR+ were included in the trial. The AC consisted of six cycles of taxotere, adriamycin, cytoxan or taxotere, epirubicin and cytoxan with the completion of radiation therapy. Patients were randomly assigned to receive TMX 20 mg/day for 5 years or up to menopause or TMX 20 mg/day for 5 years plus goserelin (GOS) 3.6 mg injection per month for 2 years. The primary end point was disease-free survival (DFS). RESULTS: Between 2003 and 2011, 101 consecutive patients were allocated to TMX (51 patients) and TMX/GOS (50 patients) groups. The mean follow-up period was 52.4 ± 2.8 months. DFS was 43.0 ± 3.6 months versus 49.9 ± 4.22 months (P = 0.13) and overall survival was 51.1 ± 3.8 months versus 53.1 ± 4.2 months (P = 0.50) in the TMX and TMX/GOS groups, respectively. The results showed 9% absolute risk reduction with respect to DFS in favor of the TMX/GOS group. CONCLUSION: This study group was comprised of stage II and III disease patients with high nodal status. The TMX/GOS combination reduced absolute risk of developing first locoregional or distant relapse by almost 9%. Longer follow-up is required to justify this protocol for routine use.

Palladium-catalyzed alkoxycarbonylation of (Z)-2-en-4-yn carbonates leading to 2,3,5-trienoates.

Pd(0)-catalyzed carbonylation of (Z)-2-en-4-yn carbonates in the presence of a balloon pressure of CO in an alcohol donates vinylallenyl esters with an exclusively E-configuration and in high yields. The fact that no such reactivity could be observed with E-configured enyne carbonates may indicate that the reaction is promoted via the cooperative coordination of palladium with both alkynyl and carbonate moieties.

Traumatic subdural pneumocephalus causing rise in intracranial pressure in the early phase of head trauma: report of two cases.

This paper presents two unique cases of subdural tension pneumocephalus which has deteriorated in the early phase of head trauma. Subdural pneumocephalus accounts for about 25% of all intracranial pneumocephalus cases. In the literature subdural pneumocephalus is describes as a benign and spontaneously resolving condition. Contrary to the available literature and our experience in 1341 trauma cases in the past ten years of whom 76 had subdural pneumocephalus, both cases deteriorated in the early hours following head trauma due to an increase in subdural air volume which was evacuated by craniotomy.

Traumatic occipital condyle fractures.

Trauma to the brain or calvaria may cause some cranial nerve damage. This may be transitory or permanent. Occipital condyle fracture (OCF) is a rarely encountered pathology not easily diagnosed by routine clinical and radiological evaluation and one of the causes of lower cranial nerve disability. Frequently, the hypoglossal nerve is involved. Here we present two cases of OCF caused by motor vehicle accidents. Both of the patients complained of dysphagia and voice disturbance. After detailed neurologic and radiologic evaluation, they were diagnosed with OCF. They were both treated conservatively. OCF as a cause of lower cranial nerve damage is rarely reported. Since it is hard to diagnose OCF by routine cranial and cervical evaluation, detailed radiological study in suspected cases is a must. Since one of our patients was admitted 6 years after the trauma, this article is also noteworthy as a report on radiological changes of the OCF.

Grisel's syndrome: a case of potentially lethal spinal cord injury in the adult.

A 22-year-old woman presented with respiratory difficulty and quadriparesis two weeks after an upper respiratory tract infection. CT showed mild (Type I) rotatory atiantoaxial subluxation, but MRI demonstrated a severely contused and oedematous spinal cord at C2-3. The case was managed conservatively with collar, steroid and antibiotics. The outcome was excellent.

External ventricular drainage for acute obstructive hydrocephalus developing following spontaneous intracerebral haemorrhages.

There is no consensus in the literature on the effects of the development of hydrocephalus on survival and disability after intracerebral haemorrhage (ICH) and the benefits of external ventricular drainage (EVD). In this open, prospective study, we investigated the clinical courses, radiological findings and outcome scores of 47 consecutive patients who were admitted to our clinic with spontaneous ICH. Hydrocephalus developed in 6 (12.8%) of the 47 patients, and EVD was applied in these 6 cases. In one of the 6 patients, the lesion was additionally excised due to the large cerebellar haematoma. Intraventricular haemorrhage was more common in patients developing hydrocephalus (83.3% vs. 29.3% in patients without hydrocephalus; p<0.05) and the lesions of all the patients were in the proximity of the ventricular system. Hospital mortality and functional outcome were not significantly different between patients with and without hydrocephalus. Our results shown that acute obstructive hydrocephalus should be anticipated if haematoma is near the ventricle or if it is opening to the ventricle. EVD is a life-saving and effective procedure that should be performed in patients who develop hydrocephalus following spontaneous intracerebral haemorrhage.

Spinal injuries in the pediatric age group: a review of 82 cases of spinal cord and vertebral column injuries.

A review of 82 children with spinal cord and/or vertebral column injury treated in our department between 1968 and 1993 showed that 67% of the patients were boys and the average age was 11.4 years. The cause, vertebral level, and type of injury, and the severity of neurological injury varied with the age of the patient. The cause of pediatric injuries differed from that of adult injuries in that falls were the most common causative factor (56%) followed by vehicular accidents (23%). The most frequent level of spinal injury was in the cervical region (57%, 47 patients) followed by the lumbar region (16.5%, 13 patients). In our series, 18% of the patients had complete injury and the overall mortality rate was 3.6%. Eleven children (13%) had spinal cord injury without radiographic abnormality (SCIWORA), whereas 39 (47%) had evidence of neurological injury. Although the spinal injury patterns differed between children and adolescents, the outcome was found to be predominantly affected by the type of neurological injury (P < 0.05). Children with complete myelopathy uniformly remained with severe neurological dysfunction; children with incomplete myelopathy recovered nearly normal neurological function. Finally, the authors conclude that most spinal injuries can be successfully managed with nonoperative therapy. The literature is reviewed as to the treatment and outcome of pediatric spinal injuries.

Angiotensin II receptor content within the circumventricular organs increases after experimental hydrocephalus in rats.

Hydrocephalus is known to cause various endocrinological abnormalities. These abnormalities are either though a direct effect on anterior hypothalamus or pituitary gland. However almost nothing is known about the effects of hydrocephalus on the intrinsic angiotensin system of the brain. The aim of this study is to investigate the effect of hydrocephalus on neurotransmitter-rich circumventricular organ systems. Such an effect was investigated by means of angiotensin receptor content in subfornical organ (SFO), organum vasculosum lamina terminalis (OVLT), area postrema (AP) and the median eminence (ME). Experimental hydrocephalus was created in rats by the intracisternal kaolin injection method as described by Shapiro et al. The receptor content was measured at 4-6 weeks by in-vitro autoradiography method as described by Israel et al. Angiotensin II receptor content in hydrocephalic animals was found to be statistically increased in SFO, OVLT and ME but not in AP when compared with the normal animals. Receptor content was found to have increased by 182.4% at SFO, 76.7% at ME, 7.7% at AP and 22.1% at OVLT after kaolin injection. These findings may indicate the possible role of CVO's on pathological conditions such as hydrocephalus.

In vivo dominant lethal effect of pyrimethamine in male mouse germ cells.

Pyrimethamine is used for treatment of malaria and toxoplasmosis. The embryotoxicity and clastogenicity of pyrimethamine is known and our aim was to investigate its dominant lethal effect in vivo. For this purpose, we used three groups of Swiss-albino male mice and a control group. We injected males with doses of 16, 32 or 64 mg/kg pyrimethamine and housed them with 10 females/male for each mating interval. Females were sacrificed and their uteri were evaluated for dominant lethality. As a result of this study we found that pyrimethamine induced dominant lethal mutations in the third, fourth and sixth weeks at the 64 mg/kg dose level, without the effect being dose-dependent. We conclude that pyrimethamine is a suspected germ cell mutagen.

Genotoxic, hematoxic, pathological, and biochemical effects of hexane on Swiss albino rats.

In the present study, the genotoxic, hematoxic effects, and their relation with pathological and biochemical parameters of hexane were investigated. Cytogenetic evaluation performed on the bone marrow indicated that chromosome aberrations increased at both hexane doses in relation to the negative controls. Decreased hematocrit, hemoglobin concentrations, and mean corpuscular volume were observed on the whole blood counts. Conjugated dienes (CD), glutathione (GSH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and catalase (CAT) were increased. Histological examinations showed intracytoplasmic vacuolisation, nuclei with lower chromatin, and parenchymatous degenerations in the dose groups. In the bone marrow slides, depletion of the erythroid series were observed. In conclusion, hexane seems to be a genotoxic and hematoxic agent leading to degeneration and lipid peroxidation in exposed groups.