IgG4-related cranio-spinal hypertrophic pachymeningitis involving the internal auditory canal.

Immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis, which is a focally or diffusely thickened dura mater and lymphoplasmacytic infiltration with increased IgG4 bearing plasma cells, is a rare disease, and cases involving the whole cervical spine are even rarer. Here, we describe a case of probable IgG4-related hypertrophic pachymeningitis involving the whole cervical spine and the auditory canals in an 18-year-old male. The patient, who had a history of paresthesia and had previously experienced weakness, presented with generalized tonic seizures. A decompressive laminectomy on cervical vertebrae was performed as a matter of urgency, removing intradural fibrous material. The patient responded well to treatment and was discharged walking independently, with no strength deficit to any of the 4 limbs, and with normal blood tests.

Accelerating orthodontic tooth movement: A new, minimally-invasive corticotomy technique using a 3D-printed surgical template.

BACKGROUND: A reduction in orthodontic treatment time can be attained using corticotomies. The aggressive nature of corticotomy due to the elevation of muco-periosteal flaps and to the duration of the surgery raised reluctance for its employ among patients and dental community. This study aims to provide detailed information on the design and manufacture of a 3D-printed CAD-CAM (computer-aided design and computer-aided manufacturing) surgical guide which can aid the clinician in achieving a minimally-invasive, flapless corticotomy. MATERIAL AND METHODS: An impression of dental arches was created; the models were digitally-acquired using a 3D scanner and saved as STereoLithography ( STL ) files. The patient underwent cone beam computed tomography (CBCT): images of jaws and teeth were transformed into 3D models and saved as an STL file. An acrylic template with the design of a surgical guide was manufactured and scanned. The STLs of jaws, scanned casts, and acrylic templates were matched. 3D modeling software allowed the view of the 3D models from different perspectives and planes with perfect rendering. The 3D model of the acrylic template was transformed into a surgical guide with slots designed to guide, at first, a scalpel blade and then a piezoelectric cutting insert. The 3D STL model of the surgical guide was printed. RESULTS: This procedure allowed the manufacturing of a 3D-printed CAD/CAM surgical guide, which overcomes the disadvantages of the corticotomy, removing the need for flap elevation. No discomfort, early surgical complications or unexpected events were observed. CONCLUSIONS: The effectiveness of this minimally-invasive surgical technique can offer the clinician a valid alternative to other methods currently in use.

The impact of osteotomy technique for corticotomy-assisted orthodontic treatment (CAOT) on oral health-related quality of life.

BACKGROUND: Corticotomy in accelerating orthodontic tooth movement, also defined as corticotomy-assisted orthodontic treatment (CAOT), is a promising technique that recently had many applications in orthodontics. AIM: The purpose of this study was to compare the use of piezoelectric surgery and conventional rotatory osteotomy technique for CAOT, determining the duration of surgery and oral health-related quality of life (OHRQoL). PATIENTS AND METHODS: CAOT was performed in a sample of subjects, randomly choosing piezoelectric surgery (PS Group) or conventional rotary osteotomy technique (RT Group). The duration of surgery was recorded and the oral health-related quality of life evaluated using the short form Oral Health Impact Profile (OHIP-14) preoperatively, 3 and 7 days after surgery. t-test and Cronbach's alpha were used for statistical analysis. RESULTS: 12 patients (mean age 14; range: 13-17) were enrolled. The time needed to complete the osteotomy cuts was greater (p = 0.1) for the piezoelectric surgery group (mean 34.3 minutes; range 35.3-32.6) than for the rotator group(mean 28.2 minutes; range 27.1-29.2). Oral health-related quality of life deteriorated from baseline (OHIP-14 mean: 6.33) to first follow-up, 3 day after surgery, in both groups (PS Group: 22.67 OHIP-14; RT Group: 21.33 OHIP-14). At 7 days follow-up there was a nearly complete recovery of the original OHIP-14 values , even faster with the conventional rotary osteotomy technique; however, no statistically significant differences were recorded between the two methods (p = 0.35). Cronbach's alpha values indicated an excellent internal consistency reliability. CONCLUSIONS: In clinical decision-making regarding the use of corticotomy-assisted orthodontic treatment, it should be aware of the expected decrease in oral health-related quality of life both using piezoelectric surgery or rotary osteotomy technique. In addition, the piezoelectric osteotomy requires a longer surgical time.

Is there a learning curve in static computer-assisted implant surgery? A prospective clinical study.

Static computer-assisted surgery (s-CAS) has been introduced to improve the results of implantology. A prospective cohort study was conducted following the STROBE guidelines to determine the presence of a learning curve in s-CAS. Six partially and six totally edentulous patients were treated by two surgeons experienced in implantology but completely inexperienced in s-CAS. Preoperative and postoperative computed tomography scans were matched to assess coronal, apical, and angular deviation and the positioning error. The accuracy data were used to evaluate the learning curve. Fifty-six implants were inserted. In partially and totally edentulous patients, the mean (range; standard deviation) coronal deviation was 0.87 (0.34-1.27; 0.35) and 1.24 (0.72-2.67; 0.79); the mean apical deviation was 1.13 (0.48-1.63; 0.39) and 1.52 (0.88-3.84; 1.15); the mean angular deviation was 2.63 (1.89-4.50; 0.98) and 3.59 (1.69-6.30; 1.65); and the mean positioning error was 0.80 (0.32-1.25; 0.35) and 1.14 (0.35-2.56; 0.77), respectively. A typical 'learning curve' effect was not identified for s-CAS.

Spindle self-organization and cytokinesis during male meiosis in asterless mutants of Drosophila melanogaster.

While Drosophila female meiosis is anastral, both meiotic divisions in Drosophila males exhibit prominent asters. We have identified a gene we call asterless (asl) that is required for aster formation during male meiosis. Ultrastructural analysis showed that asl mutants have morphologically normal centrioles. However, immunostaining with antibodies directed either to gamma tubulin or centrosomin revealed that these proteins do not accumulate in the centrosomes, as occurs in wild-type. Thus, asl appears to specify a function required for the assembly of centrosomal material around the centrioles. Despite the absence of asters, meiotic cells of asl mutants manage to develop an anastral spindle. Microtubules grow from multiple sites around the chromosomes, and then focus into a peculiar bipolar spindle that mediates chromosome segregation, although in a highly irregular way. Surprisingly, asl spermatocytes eventually form a morphologically normal ana-telophase central spindle that has full ability to stimulate cytokinesis. These findings challenge the classical view on central spindle assembly, arguing for a self-organization of this structure from either preexisting or newly formed microtubules. In addition, these findings strongly suggest that the asters are not required for signaling cytokinesis.

Fine needle aspiration cytology of thyroid nodules: conventional vs thin layer technique.

OBJECTIVE: Liquid-based cytology using the thin layer technique has recently been introduced in thyroid fine needle aspiration cytology together with or in substitution of direct smears, but its usefulness is still controversial and relatively few studies have been published in this field. The aim of the present study was to compare the results obtained from conventional smears with those from thin layer smears. DESIGN: In 3875 thyroid nodules, a double cytologic sampling was taken in randomized order, to prepare conventional or thin layer smears. MAIN OUTCOME: The diagnoses agreed in 2934 (75.7%) cases and disagreed in 941 (24.3%). The analysis of discordant data showed there were fewer non-diagnostic cases in the thin layer smears (377 vs 541, p<0.001) whereas in conventional smears there were more cases positive for carcinoma (27 vs 4, p<0.001). The cytohistologic correlation was available for 194 cases and showed that conventional smears had a greater capacity for revealing carcinomas (44 vs 31). Finally, diagnoses based on conventional smears were more sensitive than thin layer smears (93.6% vs 65.9%) whereas specificity was constant. CONCLUSIONS: From our experience, the conventional smear offers a greater possibility of diagnosis when suspecting malignancy or diagnosing malignancy cases, whereas thin layer smears significantly reduce the number of non-diagnostic cases. For this reason, we suggest combining the two techniques in routine cytologic diagnosis.

Visualization of cleavage furrow proteins in fixed dividing spermatocytes.

Cytokinesis separates the cytoplasmic organelles and the duplicated genome into two daughter cells at the end of cell division. In animal cell cytokinesis, assembly and constriction of the contractile apparatus must be finely coordinated with plasma membrane remodeling and vesicle trafficking at the cleavage furrow. Accurate control of these events during cell cleavage is a fundamental task in all organisms and is also essential for maintaining ploidy and preventing neoplastic transformation. Drosophila male meiosis provides a well-suited cell system for exploring the molecular mechanisms underlying cytokinesis, combining the powerful tools of Drosophila genetics with unique cytological characteristics. Remarkably the large size of male meiotic cells highly facilitates cytological analysis of cytokinesis. Here we describe the main procedures that we use for fixing and visualizing cleavage furrow proteins in male meiotic cells. Moreover, we detail our protocol to detect protein interactions in fixed dividing spermatocytes by applying in situ proximity ligation assay.

Minimally invasive corticotomy in orthodontics using a three-dimensional printed CAD/CAM surgical guide.

The aim of this prospective study was to evaluate the effectiveness of an innovative, minimally invasive, flapless corticotomy procedure in orthodontics. The STROBE guidelines were followed. Ten patients with severe dental crowding and a class I molar relationship were selected to receive orthodontic treatment with clear aligners and corticotomy-facilitated orthodontics. The mean age of these patients was 21 years (range 17-28, standard deviation 6.08 years); the male to female ratio was 2:1. The main outcome was a reduction in the total treatment time to correct dental crowding. The secondary outcomes were periodontal index changes, the degree of root resorption, and patient perceptions of the method used, assessed using the short-form Oral Health Impact Profile (OHIP-14). The occurrence of early surgical complications or unexpected events was also recorded. All patients completed the treatment to correct dental crowding. The average treatment time was reduced by two-thirds. The procedure did not significantly modify the periodontal indices or oral health-related quality of life. No early surgical complications or unexpected events were observed. In short, the results indicate that this new procedure is safe and accelerates tooth movement without periodontal complications or discomfort. However, the efficacy of this procedure must be confirmed in controlled clinical trials.

Minimally invasive corticotomy in orthodontics: a new technique using a CAD/CAM surgical template.

Accelerating orthodontic tooth movement is a topical issue. Despite the different techniques described in the literature, the corticotomy is the only effective and safe means of accelerating orthodontic tooth movement. Although effective, the corticotomy presents significant postoperative discomfort. The aggressive nature of these particular methods, related to the elevation of mucoperiosteal flaps and to the length of the surgery, has resulted in reluctance to proceed with this technique among both patients and the dental community. To overcome the disadvantages of the corticotomy, this technical note describes an innovative, minimally invasive, flapless procedure combining piezoelectric surgical cortical micro-incisions with the use of a 3D Printed CAD/CAM surgical guide.

Early peri-implant bone loss: a prospective cohort study.

The aim of this study was to measure the early peri-implant bone level changes before the completion of an implant-abutment connection and to evaluate the influence of demographic, biologically relevant, anatomical, and implant-specific variables on these changes. A prospective cohort study design was used. STROBE guidelines were followed. The sample comprised 493 implants placed using a two-stage surgical procedure. Random allocation was used to determine the implant placement depth. Peri-apical radiographs taken at implant insertion and at the second surgery 2 months later were matched. Kappa statistics were used to compute intra- and inter-examiner reliability. The statistical analysis was performed at the implant level. Two-way analysis of variance (ANOVA) with the Bonferroni adjusted post hoc test was used to evaluate the influence of variables. One-way ANOVA with Tukey's range test and unpaired Student t-tests were used to analyze significant variables. Early marginal bone remodelling was -0.86 mm. The timing of implant placement (P=0.00) and the depth of implant placement (P≤0.05) significantly influenced early bone remodelling. Relevant radiographic early bone loss was found, but implants initially positioned below the alveolar crest and inserted ≥3 months after tooth extraction showed statistically significant higher marginal bone loss during the healing phase.

A phase II trial of combined chemotherapy and surgery in stage IIIA non-small cell lung cancer.

A poor prognosis for patients with Stage IIIA clinical N2 treated by surgery alone has led clinical researchers to find a new treatment modality to improve the curative potential of surgery. Many Phas II trials have been carried out with induction chemo- or chemo-radiotherapy prior to surgery. From June 1988 to July 1991, 46 patients with non-small cell lung cancer (NSCLC) Stage IIIA clinical N2 entered a Phase II induction-chemotherapy trial. Patients received 2-3 cycles of high-dose cisplatin and etoposide. Forty-five were evaluable for response; the response rate was 82% (37/45: 3 CR, 34 PR). Toxicity was primarily hematologic. Surgical resection was performed in 35 patients; radical resection was possible in 28 patients (62%); three patients were incompletely resected and two patients were only explored. Three deaths were surgery-related. Median survival was 24.5 months with a 2-year survival of 53%. Cisplatin with etoposide is an active and safe induction chemotherapy regimen for NSCLC Stage IIIA N2 with a high response rate. The median survival seems to be prolonged and therefore, randomized trials are needed to compare this approach with other treatment modalities.

Relationships between the central spindle and the contractile ring during cytokinesis in animal cells.

During late anaphase and telophase, animal cells develop a bundle of antiparallel, interdigitating microtubules between the two daughter nuclei. Recent data indicate that this structure, called the central spindle, plays an essential role during cytokinesis. Studies in Drosophila and on vertebrate cells strongly suggest that the molecular signals for cytokinesis specifically emanate from the central spindle midzone. Moreover, the analysis of Drosophila mutants defective in cytokinesis has revealed a cooperative interaction between the central spindle microtubules and the contractile ring: when either of these structures is perturbed, the proper assembly of the other is disrupted. Based on these results we propose a model for the role of the central spindle during cytokinesis. We suggest that the interaction between central spindle microtubules and cortical actin filaments leads to two early events crucial for cytokinesis: the positioning of the contractile ring, and the stabilization of the plus ends of the interdigitating microtubules that comprise the central spindle. The latter event would provide the cell with a specialized microtubule scaffold that could mediate the translocation of plus-end-directed molecular motors to the cell's equator. Among the cargoes transported by these motors could be proteins involved in the regulation and execution of cytokinesis.

Long-term results in patients with advanced epithelial ovarian carcinoma treated with a combination of cisplatin, doxorubicin, and cyclophosphamide.

From 1984 to 1988, thirty-nine untreated patients with epithelial ovarian cancer received Cisplatin 50 mg/m2, Doxorubicin 50 mg/m2, and Cyclophosphamide 750 mg/m2 (CAP), at 3 weekly intervals. All patients had FIGO stage III or IV tumors except 2 patients with stage IIb and IIc, respectively. After initial surgery 23 patients had residual disease > 2 cm in diameter. Twenty-five patients (64%) were evaluable for response to chemotherapy. Objective responses were observed in 13 out of 25 patients (52%, 95% confidence intervals (CI), 32.42% to 71.58%), 6 patients had a cCR (24%) and 7 had a cPR (28%). Seventeen out of the 39 patients (44%) had a second-look laparotomy. A pCR was achieved in 5 out of 17 patients (29%); a pPR was obtained in 8 patients (47%). Median duration of survival was 41,5 months (range 2-107+); median duration of time to failure was 21 months (range 2-107+). Median disease-free survival was 86 months (range 3,5-107+). Eleven patients (28%) are alive and 9 patients (23%) are free of recurrence at median follow-up of 86 months. Only 4 of 11 long-term survivors had a pCR. In univariate analysis, histology, clinical response to chemotherapy, and the presence of ascites at the time of diagnosis, achieved a significant correlation with survival and time to failure (TTF); in addition, TTF was significantly affected by pathological response to induction chemotherapy. The only important predictors of disease-free survival (DFS) were tumor grade and stage of disease. In multivariate analysis, the presence of ascites was the only significant prognostic factor with respect to survival and TTF. Our study confirms the effectiveness of CAP in the treatment of epithelial ovarian cancer and the relatively poor long term prognosis.

Induction chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (CAP) in a combined modality approach for locally advanced and inflammatory breast cancer. Long-term results.

Thirty-one patients with locally advanced and inflammatory breast carcinoma (stage IIIA and IIIB) were treated with a combined modality approach between 1985 and 1989. All patients received as induction chemotherapy a combination of cisplatin, doxorubicin, and cyclophosphamide (CAP). Responsive patients and patients with operable stable disease underwent modified radical mastectomy followed by concurrent radiotherapy and CMF (cyclophosphamide, methotrexate, 5-fluorouracil) adjuvant chemotherapy. Thirty patients were evaluable for response to CAP. The rate of objective response to induction chemotherapy was 76.7% with 2 patients (6.7%) obtaining a complete response and 21 patients (70%) a partial response. Twenty-five patients were rendered disease-free after induction chemotherapy and surgery. Only 2 of these had pathological complete response (8%). The median overall survival was 48.7 months, the median time to progression was 22.4 months and the median disease-free survival was 29.1 months. The patients with noninflammatory breast tumor had a significantly better overall survival, disease-free survival, and time to progression. The overall survival and the time to progression were statistically superior in patients with primary tumor size < or = 8 cm. At a median follow-up of 6 years, 29% (95% CI, 13.05 to 45.01) of patients were alive and 28% (95% CI, 10.4 to 45.6) were disease-free. This combined modality treatment seems feasible with quite acceptable toxicity; the CAP combination is an effective alternative to the other standard chemotherapeutic regimens. Our results, although encouraging, are still poor, and new drugs and strategies are required to improve the long-term outcome.

Primary eyelid plasmacytoma.

We report a case of eyelid plasmacytoma. The patient presented with a superficial lesion on the upper left eyelid, 10x7 mm in size. Histological and immunohistochemical findings were indicative of plasmacytoma with slightly abnormal sub-epidermic plasma cell infiltrates. Immunoperoxidase staining was strongly positive for intracytoplasmic kappa light chains. No infiltration by atypical plasma cells could be documented in the bone marrow biopsy and aspirate. Skeletal survey showed no osteolytic lesions or osteoporosis. The tumor on the left eyelid was surgically removed. No radiotherapy was administered.

Hepatoid carcinoma of the stomach: is it still an unusual anatomo-clinical entity? Six cases-report.

Hepatoid carcinoma of the stomach is a rare neoplasm (especially in western countries) characterized by high levels of serum alpha-fetoprotein (AFP), the presence of "hepatoid foci" inside the gastric tumor and poor prognosis, due to the earlier onset of liver metastases. We treated six patients for hepatoid carcinoma of the stomach between 1990 and 1997. The female to male ratio was 1:1, the average age was 71 (54-81) and the average AFP-level was 1160 ng/ml (603-1531). We performed 2 total gastrectomies, 2 subtotal gastrectomies and 2 gastro-jejunostomies (due to presence of liver metastases): in one case, the patient underwent a splenectomy as well. All the tumors showed the presence of "hepatoid foci" (the morphological feature is close to the hepatocellular carcinoma) and a positive immunoreactivity to AFP. The mean survival was 3 months: only one patient is still alive and disease-free (with a 52 months follow-up). After radical surgery, she underwent a chemotherapic treatment with cisplatin, epirubicin, 5-fluorouracil and l-leucovorin. We conclude that our series (the widest in Italy and one of most impressive in Europe) confirm the poor prognosis of this neoplasm, but we also want to underline that this tumor is not so "unusual" any more and it requires new types of treatment, like postoperative chemotherapy, besides surgery, to be fighted properly.

Cytodiagnosis of gastric cancer by brushing: 1978-1983.

A total of 1652 endoscopic cytologic brushings from 1131 patients, 823 males aged 15 to 87 years and 358 females aged 21 to 88 years, were examined. From these we diagnosed 96 carcinomas, 69 in males and 27 in females. In 1621 samplings from 1151 patients it was possible to compare the cytologic and histologic diagnoses. To evaluate the diagnostic accuracy of both methods, brushing and biopsy, used separately or in association, we analyzed 81 cases where gastric cancer was confirmed by histologic examination of the removed stomach. The sensitivity rate of the cytodiagnosis was 88.3% and that of histology was 93.4%. Combining the two methods gave a sensitivity yield of 96.2%. These values are among the highest reported in the literature and confirm the utility of combining both methods for diagnosing gastric carcinoma.

Fine-needle aspiration cytodiagnosis of the "cold" thyroid nodule.

The results of 1886 fine-needle cytoaspirations of solid, palpable thyroid nodules, "cold" on scintiscanning, performed between 1 January 1978 and 31 December 1986, were analyzed. In total 36 diagnoses of malignancy were made (1.9%). The results of cytologic and histologic examinations were compared in 114 cases to verify the diagnostic accuracy of this method; there was agreement in 98 cases and discordance in 16 consisting of 13 false negatives (11.4%) and 3 false positives (2.6%). The sensitivity was 77.9%, specificity 94.5%, positive predictive value 93.8%, negative predictive value 80% and test efficiency 86%. These values are in the range of those reported in the literature and confirm the validity of fine-needle aspiration cytology in the preoperative diagnosis of thyroid neoplasms.

Interferon plus ursodeoxycholic acid versus interferon in the treatment of chronic C viral hepatitis.

BACKGROUND: The aim of as study was to ascertain whether the association of interferon alpha-2a and ursodeoxycholic acid (IFN+UDCA) was more efficacious in ameliorating liver parameters than interferon (IFN) alone in patients with chronic hepatitis C. METHODS: Forty-one chronic hepatitis C patients, who had at least twice the normal value of one transaminase, were randomly assigned to treatment with IFN + UDCA (n = 21) or IFN alone (n = 20). IFN was administered subcutaneously at a dose of 3 MU thrice weekly, UDCA orally at 10 mg/kg bw/day. IFN therapy was terminated 6 months later and the responders (normalized transaminases) of both groups were treated with UDCA alone for a further 12 months. RESULTS: In the IFN + UDCA group there were 2 drop-outs from therapy and 11 responders, while in the IFN group they were, respectively, 3 and 10. Transaminases normalized after the first month of treatment in 7/11 responders with IFN + UDCA compared with 3/10 in the IFN responders group. The trend to normalization was more rapid with IFN + UDCA than with IFN alone (chi 2t = 3.95; p < 0.05). Disease relapse (defined as at least one transaminase > x 1.5 the normal value) was 3/11 in the IFN + UDCA group and 4/10 in the IFN group. 2/11 responders in the IFN + UDCA and 1/10 in the IFN group were HCV RNA negative by PCR. The total Knodell histological score decreased more in the IFN+UDCA than in the IFN group (-2.67 +/- 3.44. vs -1.67 +/- 2.16, mean +/- SD). CONCLUSIONS: The administration of UDCA determine an earlier normalization-time of transaminases in the patients responders to IFN therapy and could be useful to reduce the relapse into disease after the IFN therapy.