Biochemical consequences of 5-fluorouracil gastrointestinal toxicity in rats; effect of high-dose uridine

Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more effective, doses of the drugs. It has been demonstrated that delayed high-dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster regeneration of the bone marrow. We studied the biochemical consequences of the gastrointestinal toxicity caused by 5-fluorouracil and the potential of high-dose uridine treatment to influence these adverse effects. 5-Fluorouracil caused dose-related decreases in the biochemical parameters (thymidine kinase, sucrase, maltase, alkaline phosphatase) selected as early markers of the impaired metabolic activity of the intestinal mucosa. The nadir of the biochemical changes was reached between 24 h and 72 h after 5-fluorouracil treatment, and complete regeneration of the mucosa took 6–7 days. Delayed high-dose uridine administration failed to mitigate the severity of the gastrointestinal damage that ensued after 5-fluorouracil treatment, but caused significantly earlier regeneration of the mucosa.     

Partial deletion of short arm of chromosome 8

46, XY, del(8) (p21-pter) aberration was found in a 5 year old boy with moderate craniofacial dysmorphia, mental and somatic retardation. The cytogenetic and clinical features of the patient were compared to 11 cases found in the literature. Partial 8p monosomy does not produce a unique phenotypic alteration. Postnatal growth deficiency, craniofacial dysmorphia and mental retardation are the main and common characteristics of many structural autosomal aberrations. The importance of cytogenetic analysis in such cases is stressed.     

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

Neuropsychological predictors of self-neglect in cognitively impaired older people who live alone.

OBJECTIVE: The authors examined the accuracy of certain neuropsychological tests in the prediction of harm resulting from self-neglect in cognitively impaired seniors who lived alone. METHODS: The study included 130 participants, aged 65 and older, who scored less than 131 on the Dementia Rating Scale. Neuropsychological tests were administered at baseline, resulting in eight predictive scores. Informants and primary care physicians provided information about harm that occurred to the participants during the 18-month prospective follow up. An incident was defined as harmful if it occurred as the result of self-neglect or disorientation and resulted in physical injury or property loss or damage and required emergency interventions. Proportional hazard regression analysis was conducted to examine the predictive relationship between the eight neuropsychological tests and time to incident harm with age, sex, education, the Charlson Comorbidity Index, and the Mini-Mental State Examination included in the model as covariates. RESULTS: Twenty-seven participants experienced harm during the 18-month follow-up period. A proportional hazards model indicated that three neuropsychological tests, which measured recognition memory, executive functioning, and conceptualization, were independent risk factors for harm. CONCLUSIONS: These findings provide insight into why harm occurred in these cognitively impaired elders who lived alone. They also support the ecologic validity of these tests and suggest directions for the development of intervention strategies for harm prevention.     

Distribution of tyrosine-hydroxylase (TH)-immunoreactive neurons in the diencephalon of the pigeon (Columba livia domestica)

The distribution of tyrosine-hydroxylase (TH)-immunoreactive cell bodies and fibers in the diencephalon has been investigated with immunohistological techniques in the pigeon. The results suggest that TH is present in a number of morphologically distinct neuronal systems. Preoptic and hypothalamic TH neurons were subdivided into a medial periventricular and a lateral group. The medial group starts with a rostral collection of small cells in the preoptic region. A significantly larger collection of TH neurons occupies the paraventricular nucleus (PVN) (stratum cellulare internum) and mainly consists of large multipolar cells. Further caudally, the main concentration of cells is in the hypothalamic posteromedial and the periventricular regions of the tuberoinfundibular (arcuate) nucleus. No TH neuron was found in the ventral and lateral parts of the tuberoinfundibular region, suggesting that the prominent tuberoinfundibular dopaminergic system described in mammals is absent in the pigeon. This further substantiated by the relative scarcity of TH immunoreactive fibers and varicosities in the neurohemal zone of the median eminence (ME). The caudalmost components of the medial group appear to be continuous with the large population of TH neurons distributed in the midline of the mesencephalon. Tyrosine-hydroxylase-immunopositive cells have not been found in the paraventricular organ. The lateral group consists of TH neurons loosely arranged in the lateral hypothalamus, including regions of the supraoptic nucleus and hypothalamic posterolateral nucleus. Tyrosine-hydroxylase containing neurons vary widely in size, shape, and dendritic arborization in each diencephalic region. However, it is possible to distinguish two main cell types. Small bipolar neurons with two simple arborizing dendrites were concentrated in the medial periventricular system. The second type of cell is large, multipolar with four to five branching dendrites. This latter cell type occurs mainly in the lateral system and in the PVN. Major fiber bundles containing TH immunoreactivity were identified in the lateral and periventricular hypothalamus. The paraventricular organ and the organum vasculosum laminae terminalis contained the densest arborization of fibers and varicosities. In the ME, dense innervation was found in the subependymal layer. Dense arborizations of TH positive fibers and varicosities were located in the septal nuclei and the paleostriatum augmentatum.     

Coccygectomy has a favorable effect on the intensity, manifestation, and characteristics of pain caused by coccygodynia: a retrospective evaluation of 34 patients followed for 3–18 years

Background  Coccygodynia can cause severe pain and disability in patients. There are contradictions in the literature regarding the final results of coccygectomy for coccygodynia. We evaluated the long-term effects of coccygectomy on the intensity, characteristics, and manifestation of pain caused by coccygodynia to determine the adequacy of operation among treatment modalities. Materials and methods  Thirty-four patients with coccygodynia were treated by coccygectomy. In 22 cases, trauma, and in one case childbirth was the cause. 11 cases were regarded as idiopathic. The intensity, characteristics of pain, and the most painful activities were evaluated at an average of 7.6 (3–18) years of follow-up time. Results  Before the operation, all 34 patients had pain while sitting, moreover, 26 of them had pain during standing, walking, at night or a combination of these. 21 patients had intolerable or very intensive, mainly acute, sharp or burning pain. 11 patients had dyschesia, 2 had dysuria and 6 had dyspareunia. At follow-up, 7 patients were completely free of pain, 15 others had moderate, 11 medium, and only one patient had severe, but none had intolerable pain. Only seven patients had acute, sharp or burning pain postoperatively. The decrease of average pain score from 8.0 to 3.2 was significant (P < 10⁻¹²). The number of the patients with dyschesia and dyspareunia decreased from 11 to 7 and from 6 to 3, respectively. Two patients had dysuria, but their complaints did not change after the operation. One of the two patients who needed reoperation had an excellent final result, while the other remained unchanged. 12 and 16 patients (together 82%) regarded the final result of the operation excellent and good, respectively. The condition of five others did not change, while one became worse. The patients with younger age, smaller body mass index, and less co-morbidities had better final result. There were no serious complications. Conclusion  Coccygectomy for coccygodynia is a safe method to decrease the intensity of pain and other complaints of the patients. The operation can be the choice of treatment if conservative measures fail.     

Local excision for ypT2 rectal cancer--much ado about something.

BACKGROUND: The role of local excision for pT2 distal rectal cancer has been challenged because of the observation of high rates of lymph node metastases and local failure. However, neoadjuvant chemoradiation therapy (CRT) has led to increased local disease control and significant tumor downstaging, possibly decreasing rates of lymph node metastases. In this setting, a possible role for local excision of ypT2 has been suggested. METHODS: A total of 401 patients with distal rectal cancer underwent neoadjuvant CRT. Tumor response assessment was performed after at least 8 weeks from CRT completion. One hundred and twelve patients with complete clinical response were not immediately operated on and were excluded from the study, and 289 patients with incomplete clinical response were managed by radical surgery. Patients with final pathological stage ypT2 were analyzed to determine the risk of unfavorable pathological features that could represent unacceptable risk for local failure after local excision. RESULTS: Eighty-eight (30%) patients had ypT2 rectal cancer. Final ypT status was not associated with pretreatment radiological staging (p = 0.62). ypT status was significantly associated with the risk of lymph node metastases, risk of perineural and vascular invasion, and recurrence (p = 0.001). Lymph node metastases were present in 19% of patients with ypT2 rectal cancer. The risk of lymph node metastases in ypT2 was associated with the presence of perineural invasion (47% vs 4%; p = <0.001), vascular invasion (59% vs 6%; p < 0.001), and decreased mean interval CRT surgery (12 vs 18 weeks; p < 0.001), but not with mean tumor size (3.2 vs 3.1 cm; p = 0.8). Disease-free and overall survival rates were significantly better for patients with ypT2N0 (p = 0.02 and 0.006, respectively). Fifty-five (63%) patients with ypT2 had at least one unfavorable pathological feature for local excision (lymph node metastases, vascular or perineural invasion, mucinous type or tumor size >3 cm). CONCLUSION: Lymph node metastases were present in 19% of patients with ypT2 and were significantly associated with poor overall and disease-free survival rates. The risk of lymph node metastases could not be predicted by radiological staging or tumor size. Radical surgery should be considered the standard treatment option for ypT2 rectal cancer after CRT.     

Surgical treatment of intercostal hernia with implantation of polypropylene mesh

The intercostal hernia of the lung is a very rare extraordinary disease that requires operation because of the complaints and potential complications. The authors review cases of their operations and analyze the subsequence and treatment. Three patients have been treated for intercostal lung hernia in our treatment. The causes of this disease were a previous thoracotomy in one case and fits of coughing in the other two cases. The diagnosis was set up on the grounds of the specific clinical symptoms, thoracic X-ray and CT scan. The hernia was dissolved with percostal stitches and with the suture of the thoracic musculature in two cases. Plastic operation of the thoracic wall by implanting a polypropylene surgical mesh (Prolen, Ethicon, Johnson & Johnson) was performed in the case of the third patient and later in the first two patients due to recrudescence. In one case the authors were constrained to resect the dystelectasial lung in the hernial sac. The three patients had been operated five times. Relapse of hernia was detected in two patients, in whom the intercostal space had been reconstructed with percostal stitches. We did not detect any relapsing in those two patients at 33 and 66 months after the second operation with mesh implantation. The third patient who got mesh implant immediately did not relapse 12 months after the operation. Intercostal lung hernia is an indication of operation. A plastic operation of the thoracic wall combined with the implantation of a surgical mesh is recommended to close the hernial orifice, which is suitable for treating both primary and relapsed hernias. Recurrence is rare in those patients treated with this method.     

Synthesis of N-(phosphonoacetyl)-dipeptide derivatives and evaluation of their antihypertensive activity

A series of N-(phosphonoacetyl)-dipeptide derivatives was synthesized for pharmacological testing as antihypertensive compounds. Several of these compounds demonstrated a moderate antihypertensive effect in Wistar spontaneous hypertensive rats (SHR) with p.o. dosing. ACE inhibition by the compounds was studied using ACE from rat plasma and lung. Inhibitors containing esterified C-termini are pro-drugs and showed activity only for plasma ACE.