Late effects of intraoperative radiotherapy]

One group (145 isolates) of Neisseria gonorrhoeae was collected from municipal clinics in Bloemfontein in 1994 and a second group (65 isolates) in 1995. Penicillin and tetracycline MICs were determined and plasmid analysis performed to monitor antimicrobial susceptibilities in conjunction with the occurrence of plasmids in these isolates. The prevalence of penicillin resistance caused by beta-lactamase plasmids remained constant at 9% during the study period. Three high-level tetracycline-resistant strains (MICs 16 mg/L), the first to be detected in South Africa, were isolated in 1994. Although there was a reduction in the percentage of isolates harbouring 24.5 MDa conjugative plasmids (from 79% in 1994 to 46% in 1995), this was partially counteracted by an increase in TetM-encoding conjugative plasmids (25.2 MDa) from 2% to 18.5%. The tetM genes of 13 isolates shown to exhibit high-level tetracycline resistance were characterized as the American type. The American-type tetracycline resistance plasmid was demonstrated in 11 isolates. Digestion with Bg/l showed that two isolates harboured tetM-encoding plasmids that differed from the American- and Dutch-type plasmids described previously: one isolate contained a plasmid that produced two fragments of different sizes from those of the American-type plasmid and the second isolate possessed an American/Dutch hybrid plasmid. Auxotyping/serotyping and random amplified polymorphic DNA analysis revealed a predominant tetracycline-resistant family (NR/IA-6, genomic group I) in Bloemfontein. As there is a high incidence of chlamydial infections in southern Africa requiring tetracycline therapy, selective pressures exist in the environment for the maintenance and rapid spread of high-level tetracycline-resistant N. gonorrhoeae. It is possible that tetM genes may have emanated from Botswana and/or Namibia to Bloemfontein. The establishment of high-level tetracycline-resistant N. gonorrhoeae in Bloemfontein was seen to be complex as a related group of strains was identified, plasmid dissemination was evident and two new TetM-encoding plasmids were demonstrated. The appearance of these TetM-encoding plasmids indicates either that the American- and Dutch-type plasmids are continuing to evolve or that tetM genes are being introduced into different families of 24.5 MDa conjugative plasmids.     

Late effects of radiotherapy on the neuroendocrine system

When the hypothalamic-pituitary axis (HPA) is included in the treatment field in children and adults, a variety of neuroendocrine disturbances are more common than has been appreciated in the past. Clinical damage to the pituitary and thyroid glands usually occurs months to years after treatment, and is preceded by a long subclinical phase. Primary brain tumors represent the largest group of malignant solid tumors in children. The survival rates of 50% reported in the literature are achieved at the expense of late occurring effects. Radiation-induced abnormalities are generally dose-dependent. Growth hormone deficiency and premature sexual development can occur at doses as low as 18 Gy in conventional fractionation, and is the most common neuroendocrine problem in children. In patients treated with > 40 Gy on the HPA, deficiency of gonadotropins, thyroid stimulating hormone, and adrenocorticotropin can be found. Following high-dose radiotherapy (> 50 Gy), hyperprolactinemia can be seen, especially among young women. Most neuroendocrine disturbances that develop as a result of HPA can be treated efficiently, provided that an early detection of these endocrine dysfunctions abnormalities is done.     

食管癌后程三维适形放疗的临床疗效评价

Objective:The aim of our study was to evaluate the clinical results and acute side effects of late course three-dimensional conformal radiotherapy (3DCRT) for esophageal carcinoma.Methods:From January 2004 to October 2006,70 patients with esophageal carcinoma received late course 3DCRT.Their clinical data were analyzed retrospectively.The short-term clinical results,acute side effects,local control rates and survival rates were evaluated.Results:The complete response rate was 62.9%,partial response rate was 35.7%,and the overall response rate was 98.6%.The 1-,2- and 3-year local control rates were 77.1%,51.4% and 45.7%,respectively.The 1-,2- and 3-year overall survival rates were 75.7%,54.3% and 38.6%,respectively.The median survival time was 26 months.Conclusion:The technique of late course 3DCRT is an effective treatment for esophageal carcinoma and tend to improve the overall survival rate.     

Late sequelae of oncologic treatment in children

The risk of late effects of cancer treatment in children is higher than that after treatment during adulthood. The late effects of chemotherapy are proportional to the dosage and those of irradiation to the size of the radiation field, fractionation and dose. Irradiation may lead to impaired growth of bone and soft tissues, cranial irradiation to pituitary deficiencies, alopecia and impaired cognitive function, irradiation of the neck to altered thyroid function, thoracic irradiation to diminished pulmonary function and cardiovascular morbidity, radiation therapy of the abdomen to infertility in females, impaired renal function and chronic enteritis. Chemotherapy-induced damage is more organ-specific. Well-known cardiotoxic agents are the anthracycline derivatives. Restricted pulmonary function is seen after treatment with bleomycin and nitrourea derivatives. Several antineoplastic agents are gonadotoxic in men. Nephrotoxic agents are cisplatin and ifosfamide. The cumulative relative risk of developing a second primary neoplasm is 3,8-6,9 after a follow-up period of 25 years. Alkylating agents and the topoisomerase inhibitors are known to increase the risk of haematologic malignancy, while radiation therapy is associated with bone, soft tissue, thyroid, breast, brain and gastrointestinal malignancies.     

Late complications of radiotherapy. Role of the time factor

Purpose of the study was to determine the prevalence of toxoplasma infection among the pregnant women and their newborn infants in Chengdu and to identify risk factors of acquiring toxoplasma infection. The Maternal and Child Health Hospital was selected by random cluster sampling method in the study. Each pregnant women admitted to the above hospital consecutively and her surviving newborn at birth were included in this survey. History, physical examination and blood specimens were obtained from 1,211 pairs of mother-newborns. ELISA was used to detect toxoplasma IgG and IgM antibodies. Results revealed that sera prevalence of toxoplasma IgG antibodies and IgM antibodies of pregnant women were 39.14% and 4.21% respectively. Seraprevalence of toxoplasma IgM antibodies of newborn infants was 1.07%. Congenital malformation of newborn infants may be associated with congenital toxoplasma infection (P < 0.05, OR = 6.32).     

Late effects in survivors of bone tumors

Today more than 71% of children with cancer are surviving their disease. This is because of improved treatment including aggressive combination therapy and better supportive care measures. The majority of patients with bone tumors are now being treated with surgery, chemotherapy, and radiation therapy, resulting in an increase in numbers of long-term survivors. This aggressive therapy, however, has increased the risk of developing late effects. This article reviews some of these late effects in survivors of bone tumors diagnosed in childhood or adolescence. Areas that are explored include cardiac, infections, second operations, second malignant neoplasms, renal, auditory, fertility, pulmonary, functional, and psychosocial outcomes. The need for long-term follow-up clinics is also addressed.     

Late complications after surgery of acute appendicitis in children

The causes of the late complications of appendicular peritonitis were analyzed in 48 patients (20 of them were previously operated on in the clinic, 28--in other hospitals). The principles of treatment, follow-up results, the complications prophylaxis are expounded.     

Late local recurrence after radiotherapy for tongue and early glottic carcinoma

BACKGROUND/AIM: Late local recurrence after radiotherapy for tongue and early glottic carcinoma is rarely discussed. In the head and neck cancer, approximately 90% of local recurrence occurred within 2 years after radiotherapy. However, we found that late local recurrence after radiotherapy for glottic cancer was not rare. Our aim was to evaluate the late local recurrence after radiotherapy for early glottic and tongue cancer. PATIENTS AND METHODS: From 1967 through 1982, 633 patients with tongue carcinoma and 330 patients with early (T1T2N0) glottic carcinomas were treated at the Department of Radiology, Osaka University Hospital. Of these 821 patients, 329 patients with tongue carcinoma and 221 patients with early glottic carcinoma survived at 5 years after radiotherapy without local recurrence. For tongue carcinoma, patients were divided by T category. For early glottic carcinoma, patients were divided by the tumor response at 40 Gy. RESULTS: Late local recurrence occurred in 23 of 329 patients (7%) with tongue carcinoma, and in 9 of 221 (4%) with early glottic carcinoma. For tongue carcinoma, late recurrence occurred in 19 of 249 patients (8%) in stage I and II, and 4 of 80 patients (5%) in stage III and IV. For glottic carcinoma, late recurrence occurred in 8 of 137 patients (6%) with tumor clearance at 40 Gy and 1 of 63 patients (2%) with tumor persistence at 40 Gy. The incidence of double cancer was also evaluated. Of 329 5-year survivors with tongue carcinoma, 39 patients (12%) had another malignancy, and 26 patients of 221 5-year survivors with early glottic carcinoma (12%) had also another malignancy. Of 39 double primaries of tongue carcinoma, 10 patients (26%) had head and neck malignancies, and none of 26 double primaries of early glottic carcinoma. CONCLUSION: Late local recurrence was not rare in tongue and early glottic cancer. Poor prognostic group showed lower incidence of late recurrence than good prognostic group. This result suggests that secondary tumor at the same site of primary tumor is late local recurrence.     

Late effects of radiations on the esophagus

PURPOSE: To describe the clinical course of oculoglandular tularemia with acute glaucoma and corneal oedema. METHODS: Clinical course, results of laboratory assays and treatment of oculoglandular tularemia in a 58-year-old woman. RESULTS: The patient had acute glaucoma and corneal oedema in connection with acute tularemia. At the onset of the disease she had a fever (39 degrees C), pains in her muscles and in her right eye. The intraocular pressure, which was 68 mmHg at the beginning was lowered with intravenous and per oral acetatcolamide together with timolol and pilocarpine eyedrops, and because of a narrow anterior chamber, with subsequent laser iridotomies. The tularemia was treated with ciprofloxacin 500 mg twice daily for ten days. Vision was finger counting at the beginning of the disease. The corneal oedema gradually subsided and vision normalized during the two-month follow-up. CONCLUSION: Oculoglandular tularemia was connected with acute glaucoma and corneal oedema.     

Neuropsychological outcome of children after radiotherapy for intracranial tumours

With the aim of determining the neuropsychological disturbances associated with cranial radiotherapy in the child, a cross-sectional study was carried out on 25 survivors of medial-edge intracranial tumours. Children irradiated for intracranial tumours experienced deterioration mainly in visual attention and memory, but also in verbal fluency, full-scale IQ, and performance IQ and all its subtests, compared with control groups. This deterioration progressed with time, finally involving at least abstract thought and verbal skills. The pattern of damage by irradiation varied according to the degree of brain maturity, therefore the younger the child at irradiation, the greater the decline in IQ and visual-constructive abilities, and the earlier the deterioration of visual memory and verbal skills.     

Late feedback effects of hypothalamic-pituitary-adrenal axis hormones in healthy subjects

The main aims of the present study were to establish an in vitro/in vivo correlation for multiple-unit capsules of paracetamol by means of statistical prediction models and to investigate the effect of a number of in vitro variables on the discussion rate of paracetamol from the formulation. A fractional factorial screening design was used to investigate the effects of the variables agitation, pH, osmolality, viscosity, and the presence of bile salt on the dissolution rate of paracetamol. The effects were evaluated in two separate partial least-squares models, in which the responses were expressed as the cumulative percentage of paracetamol dissolved at specified time-points (model I) and as the shape (beta) and scale (eta) parameters according to the Weibull function (model II). It was concluded that agitation and viscosity had significant effects on the dissolution rate of paracetamol. Statistical models based on the responses from models I and II were then used to predict the in vitro conditions most closely correlated with the in vitro dissolution of paracetamol after administration of the formulation to 10 healthy volunteers. The predicted optimal in vitro conditions were similar for the two models and not too far from what is expected from the gastrointestinal tract. The experimental verification of the in vitro conditions showed that both models were equally good, and contributed to high degrees of correlation with the in vivo dissolution behavior of the formulation during 9 hr. The relationships obtained when plotting the percentage dissolved in vitro versus in vivo were y = 1.1x (r2 = 0.98) and y = 1.1x (r2 = 0.94) for models I and II, respectively. Based on these results, it is difficult to state a preference for one of the models. Finally, the use of statistical prediction models to develop critical in vitro tests is a successful approach in the establishment of associations between dissolution behavior in vitro and in vivo for oral extended-release systems.     

Coarctation of the aorta in children. Late results after surgery

From 1960 to 1970, 110 patients underwent operation for coarctation of the aorta. The overall mortality was 23%. However, in infants operated on at less than 6 months of age, the mortality was 63%, whereas there was only a 4% mortality in those operated on after 6 months of age. Late follow-up was available in 87 patients from five to 15 years postoperatively. There was a 14% frequency of recoarctation in the group of long-term survivors. Systemic hypertension, defined as an upper extremity blood pressure greater than 140/90 mm Hg, was found in 23% of the survivors. This study has demonstrated a significant frequency of postcoarctectomy hypertension and residual hemodynamic and angiographic abnormalities in patients without clinical evidence of recoarctation. This indicates the need for continued long-term follow-up of these patients.     

Late effects of treatment for early-stage Hodgkin's disease

A comprehensive survey of late effects (physical, social and reproductive) following treatment at a single institution for early stage Hodgkin's disease (HD) was performed. A total of 611 patients with stage I and II HD treated between 1973 and 1984 were reviewed; 460 were alive and were mailed a self-reported questionnaire. A total of 363 (79%) replies were received. Twenty patients died of second malignancy, 14 of heart disease and nine from respiratory disease. There were 37 cases of second malignancy [relative risk (RR) 2.2, absolute excess risk (AR) 35.8]. The 15-year incidence of heart disease was 11% and there were nine myocardial infarction deaths (RR 1.55, AR 5.4). Twenty-eight (8%) respondents stated that their career had been greatly interfered with, 53 (14.5%) perceived financial loss. Sexual activity was disrupted in 25.8%. In total, 56 men had fathered 112 pregnancies. Of 171 women, 40.3% became pregnant, resulting in 92 live births. A total of 43 men and 16 women had sought medical advice with regard to infertility.     

Late results of the complex treatment of primary kidney neoplasm in children

88 children with primary renal tumours (85 with nephroblastoma and 3 with renal cell carcinoma) were treated between 1973 and 1990 in the paediatric urology department of Institute "Pirogov" and the paediatric haematological oncology department in Sofia. Combined therapy includes early surgery (nephrectomy + lymphadenectomy) and combination chemotherapy (Dactinomycin, Vincristine + Adriamycin, Endoxan). Stage II (with lymph node in involvement), III and IV disease was treated by radiotherapy. Chemotherapy and preoperative radiotherapy were administered in the case of very large tumours. In this series of 88 children, 64 (72.2%) are alive and 21 (23.8%) have died, while no information was available for 3 cases (3.5%). Survival was related to clinical stage, histological type and the child's age. One of the 2 cases with bilateral tumours survived for more than 2 years after the operation and combined therapy. One girl with liver and spleen metastases survived in remission for 11 years after the operation. Two children with pulmonary metastases, discovered one year after surgery for the primary tumour survived in remission for 4 and 14 years, respectively. The authors discuss the good results obtained with early combined therapy in this type of tumour.     

Preliminary results of treatment of solid tumors in children with non-standard radiotherapy]

Urinary excretion of mefenamic acid (MA) and its two oxidative metabolites, M-I (3'-hydroxymethyl derivative) and M-II (3'-carboxyl derivative), and their glucuronides was investigated in preterm infants undergoing MA therapy. MA was given orally at a dose of 2 mg/kg and the dose was repeated every 24 h a maximum of three times. Urine was collected for up to 5 d after the last dose, and MA and the metabolites were determined by a newly developed HPLC. The cumulative amounts of MA and the metabolites excreted in the urine varied from 7 to 46% of the total dose administered, and were less than those reported in adults and children. Significant correlation was observed between the plasma half-life of MA and the cumulative amount of MA and the metabolites excreted in the urine. These results suggest that long plasma half-lives of MA observed in preterm infants are due mainly to low activity of drug metabolizing enzyme(s). In an infant who received the two regimens of MA therapy about 2 weeks apart, the plasma half-life of MA was shortened and the urinary excretion of the MA metabolites including their glucuronides was greatly increased during this period. It is suggested that the activities of both cytochrome P-450(s) and glucuronyltransferase(s) related to MA metabolism rapidly increased during the first month of the infant's life.     

Late endocrine effects of ovarian electrocautery in women with polycystic ovary syndrome

Intravenous (i.v.) bolus injection of calcitonin gene-related peptide (CGRP) caused a depressor response, which was significantly larger in 12-week-old spontaneously hypertensive rats (SHR) than in Wistar-Kyoto rats (WKY). CGRP also caused decreases in carotid and hindquarter vascular resistance, the magnitude of which was larger in the carotid than the hindquarter. In both regions, the vasodilator response to CGRP was significantly larger in SHR than WKY. Plasma CGRP level was significantly lower in SHR than WKY. These results suggest that depressor and vasodilator responses to CGRP are enhanced in SHR and that decreased plasma CGRP level in SHR may contribute to the enhanced responses.     

Long-term effects of radiotherapy administered in childhood for the treatment of malignant diseases

BACKGROUND: The use of radiotherapy for the treatment of childhood malignancy has improved long-term survival significantly, and many treated children now survive well into adulthood. As a consequence, long-term effects of childhood irradiation are being seen with increasing frequency. METHODS: The medical records of 236 patients who had been treated for malignant disease with radiotherapy during childhood were examined to determine the long-term effect of the radiation on their growth and development. RESULTS: Mean treatment dose was 35.5 Gy; mean age at treatment was 7.2 years; and mean follow-up was 14.5 years. Adjuvant chemotherapy was given to 82%. Some degree of bone deformity (usually with overlying soft-tissue hypoplasia) was seen in 40%; 21% developed some type of endocrine deficiency; 30% developed atrophic skin changes; and 7% developed second malignancies. The incidence of bone deformity and hormonal deficiency increased with the radiation dose; the incidence of second malignancy was independent of dose. Bone deformities were more common when radiation was administered before the age of 2 years. CONCLUSIONS: The consequences of radiotherapy in childhood are significant and must be considered when planning treatment. Even when treatment is essential, families should be informed of the possibility of growth disturbance to prevent subsequent misunderstanding.     

Late effects of radiation on the eye and ocular adnexa

The N-methyl-D-aspartate receptor/nitric oxide synthase (NOS)/guanylate cyclase pathway, which plays a crucial role in synaptic plasticity in the brain, is modulated by ethanol. We studied the effect of ethanol in vitro on NOS in rat cerebellum and showed that ethanol (25-200 mM) inactivated NOS in a dose-dependent manner. This inactivation was prevented by the biopterin cofactor tetrahydrobiopterin (BH4) as well as by L-arginine, a NOS substrate, but not by NADPH. These results suggest that ethanol reduces NOS activity by modulating the conformation of the enzyme and thereby its stability, probably by interacting with the binding sites of BH4 and/or of L-arginine. Our data also suggest that inactivation of NOS may contribute to the decrease in the cGMP level, and thus may play a role in the pharmacological actions of ethanol in vivo.     

Acute effects of inhaled nitric oxide in children

At present, there are only two laser Doppler perfusion imaging systems (LDIs) manufactured for medical applications: a 'stepwise' and a 'continuous' scanning LDI. The stepwise scanning LDI has previously been investigated and compared with coloured microsphere determined standardised flow. The continuous scanning LDI is investigated and compared with the stepwise scanning LDI for its ability to measure in vivo, hypoaemic, ligament tissue blood flow changes. The continuous scanning system was supplied with two lasers, red and near infrared (NIR), allowing for additional assessment of the effect of wavelength on imaging ligament perfusion. Perfusion images were obtained from surgically exposed rabbit medial collateral ligaments (MCL). Continuous and stepwise LDI scans were compared using correlation and linear regression analysis of image. averages and standard deviations. Using the same method of analysis, LDI measurements using red and NIR lasers indicated a high degree of correlation, at least over the ranges of perfusion assessed, indicating that red and NIR lasers measure similar regions of flow in the rabbit MCL. These experiments confirm that both LDI techniques provide a valid in vivo measure of dynamic changes in connective tissue perfusion and could have significant impact on the understanding and treatment of joint injury and arthritis.