Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone.

The authors conducted a retrospective analysis of 1178 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. The minimum follow-up time was 3 years. The 10-year actuarial pelvic failure rate in Stage IB was 6% for tumors less than 3 cm, 15% for tumors 3 to 5 cm, and 30% for tumors more than 5 cm (P = 0.0018). The 10-year actuarial pelvic failure rate in Stage IIA was 10% for tumors less than 3 cm, 28% for tumors 3 to 5 cm, and 20% for tumors more than 5 cm (P = 0.09). Stage IIB unilateral nonbulky tumors (less than 5 cm) had a 20% pelvic failure rate compared with 28% for bilateral lesions and 35% for unilateral bulky tumors (more than 5 cm) (P = 0.35). In Stage IIB, pelvic failures were greater when disease extended into the lateral parametrium (30%) compared with medial parametrial involvement only (17%) (P = 0.01). In Stage III unilateral nonbulky tumors, the pelvic failure rate was 28% compared with 45% to 50% for unilateral bulky lesions (P = 0.002). Bilateral parametrial disease in Stage IIB did not increase the pelvic failure rate (21% in both subgroups) (P = 0.83), whereas in Stage III, bilateral parametrial involvement was associated with a 48% pelvic failure rate versus 28% for unilateral extension (P less than or equal to 0.01). Five-year disease-free survival (DFS) rates for IB tumors less than or equal to 3 cm was 90% versus 67% for tumors more than 3 cm (P = 0.01). In Stage IIA tumors less than or equal to 3 cm, 5-year DFS was 70% versus 45% for tumors more than 3 cm. Patients with Stage IIB nonbulky tumors (less than or equal to 5 cm in diameter) had better 10-year DFS (65% to 70%) compared with those with bilateral bulky tumors (45% to 55%) (P = 0.10). Stage III patients with unilateral nonbulky tumors had a 55% 10-year DFS compared with 35% to 40% for bulky tumors or bilateral parametrial involvement (P = 0.002). The authors concluded that clinical stage and size of tumor are critical factors in the prognosis, therapy selection, and evaluation of results in carcinoma of the uterine cervix.     

The functional anatomy of the muscles of facial expression in humans with and without cleft lip and palate. A contribution to refine muscle reconstruction in primary cheilo- and rhinoplasties in patients with uni- and bilateral complete CLP.

The great variation of primary cheiloplasty procedures in Cleft Lip and Palate (CLP) patients shows that there is disagreement regarding the embryonic development of this part of the face, the macroscopic and microscopic functional anatomy of the human muscles of facial expression and their role as a functional matrix for balanced and harmonious facial development. The purpose of this study is to present results of microsurgically dissected facial muscles, several parts of the nose and the human midface in specimens with and without cleft lip and palate. The results are compared with those of other investigations. Recommendations are presented for a standardized dissection technique of the facial muscles of expression for different types of primary cheilo- and rhinoplasty techniques.     

Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.      

Carcinoma of the uterine cervix. II. Lack of impact of prolongation of overall treatment time on morbidity of radiation therapy

PURPOSE: Several reports document a negative impact of prolongation of overall treatment time in a course of irradiation on tumor control and survival. A correlation has been documented of incidence of significant treatment sequelae with increasing doses of irradiation, volume of the specific organ, and dose per fraction. However, no data were found on the potential correlation of overall irradiation treatment time with significant sequelae. METHODS AND MATERIALS: Records were reviewed of 1,269 patients with carcinoma of the cervix (Stage IB to HI) treated with definitive irradiation (combination of external beam and two intracavitary insertions). Follow-up was obtained in 97% of patients (median, 12 years; minimum, 3 years; maximum, 28 years). The relationships between overall treatment time and time of brachytherapy and incidence of treatment sequelae were analyzed for each stage. RESULTS: Overall incidence of Grades 2 (moderate) sequelae was 7% and of Grade 3 (severe) sequelae, 11%. There was no significant correlation of various incidences of Grade 2 and 3 sequelae with overall treatment times (8% in patients treated in less than 7 weeks, 9% in 7.1 to 9 weeks, and 12% when treatment time was longer than 9 weeks) (p = 0.08). In patients with Stage IB and IIA tumors, incidence of rectal toxicity (mostly proctitis) was comparable in patients treated in less than 7 or 7.1 to 9 weeks (4.1 and 6%, respectively) and slightly higher in those treated in longer periods (11.5%) (p = 0.24). In patients with Stage IIB and III, the incidence of Grade 2 and 3 small bowel morbidity was 2% in those treated in less than 7 weeks, 6% for 7.1 to 9 weeks, and 4.9% for longer times (p < or = 0.01). This increased morbidity was also correlated with total dose of irradiation to the lateral pelvic wall: 5 of 257 (2%) for less than 60 Gy and 21 of 438 (4.8%) for higher doses (p < or = 0.01). There was no significant correlation between the timing of brachytherapy (usually two low dose rate intracavitary insertions performed within 4.5 to 6.5 weeks of initiation of external beam therapy) and significant treatment sequelae. CONCLUSIONS: We observed a varied average incidence of Grade 2 and 3 morbidity in the bladder, rectum, and small intestine with different overall treatment times, without a definite pattern to suggest an impact of prolongation of treatment time on morbidity. Likewise, there was no significant correlation with the timing of intracavitary insertions and morbidity of therapy. Because prolongation of the overall treatment time has a well-documented detrimental effect on pelvic tumor control and survival in carcinoma of the cervix with no significant impact on morbidity, it is imperative to deliver radiation therapy in the shortest possible time and without schedule interruptions.     

ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn’s disease patients

AIM:To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease(CD).METHODS:In this study,we assessed the differential responses in phagocytosis by measuring the phagocytic activity and the percentage of active phagocytic monocytes and granulocytes in inflammatory bowel disease patients as well as healthy controls.As both autophagy related like 1(ATG16L1)and immunityrelated guanosine triphosphatase gene are autophagy genes associated with CD and more recently nucleo-tide-binding ligomerization domain-containing protein2(NOD2)has been identified as a potent inducer of autophagy we genotyped the patients for these variants and correlated this to the phagocytic reaction.The genotyping was done with restriction fragment length polymorphisms analysis and the phagocytosis was determined with the pHrodo?Escherichia coli Bioparticles Phagocytosis kit for flowcytometry.RESULTS:In this study,we demonstrate that analysis of the monocyte and granulocyte populations of patients with CD and ulcerative colitis showed a comparable phagocytic activity(ratio of mean fluorescence intensity)between the patient groups and the healthy controls.CD patients show a significantly higher phagocytic capacity(ratio mean percentage of phagocytic cells)compared to healthy controls(51.91%±2.85%vs 37.67%±7.06%,P=0.05).The extend of disease was not of influence.However,variants of ATG16L1(WT:2.03±0.19 vs homozygoot variant:4.38±0.37,P<0.009)as well as NOD2(C-ins)(heterozygous variant:42.08±2.94 vs homozygous variant:75.58±4.34(P=0.05)are associated with the phagocytic activity in patients with CD.CONCLUSION:Monocytes of CD patients show enhanced phagocytosis associated with the presence of ATG16L1 and NOD2 variants.This could be part of the pathophysiological mechanism resulting in the disease.     

Evaluation of Efficacy of Microwave Irradiation in Disinfecting Dental Gypsum Casts: An Ex Vivo Study

The aim of this study is to assess the efficacy of microwave irradiation in disinfecting gypsum casts and also to compare its efficacy with validated method of chemical disinfection. The present study is an ex vivo study conducted on a sample of five irreversible hydrocolloid impressions in vitro and on ten patients gypsum casts in vivo following standard impression techniques to check the efficacy of microwave oven irradiation and compare its efficacy with standard chemical method of disinfection. Results were analysed using Mann–Whitney test and Wilcoxon signed rank test. Untreated gypsum casts showed cfu/ml counts with a median log value of 6, while microwave-irradiated ones had median cfu/ml counts of 0. Casts poured from chemically disinfected impressions demonstrated cfu/ml counts with a median log value of 5. Microwave irradiation was found to be effective in disinfecting gypsum casts when compared to chemical disinfectant in disinfecting dental impressions.     

Transcription-targeted gene therapy for androgen-independent prostate cancer

The Escherichia coli enzyme (purine nucleoside phosphorylase, PNP) gene is delivered directly into PC3 tumors by one injection of replication-deficient human type-5 adenovirus (Ad5). Expressed PNP converts the systemically administered prodrug, 6MPDR, to a toxic purine, 6MP, causing cell death. We sought to increase the specificity of recombinant Ad vectors by controlling PNP expression with the promoter region from the androgen-dependent, prostate-specific rat probasin (Pb) gene. To increase its activity, the promoter was combined with the SV40 enhancer (SVPb). Cell lines were transfected with plasmids containing both a reporter gene, under SVPb control, and a reference gene cassette to allow normalization of expression levels. Plasmids expressed approximately 20-fold more reporter in prostate cancer than in other cells, but surprisingly, the SVPb element was both androgen-independent and retained substantial prostate specificity. Killing by Ad5-SVPb-PNP vector of cell lines cultured with 6MPDR for 6 days was 5- to 10-fold greater in prostate cancer than in liver or lung cells. In vivo, a single intratumoral injection of Ad5-SVPb-PNP (4 x 10(8) pfu), followed by 6MPDR administration twice daily for 6 days, significantly suppressed the growth of human prostate tumors in nude mice and increased their survival compared to control animals. Thus, the androgen-independent, prostate-targeting Ad5 vector reduces human prostate cancer growth significantly in vitro and in vivo. This first example of an androgen-independent vector points the way toward treatment of emerging androgen-independent prostate cancer in conjunction with hormone ablation therapy at a time when the tumor burden is low.