Adenocarcinoma cervicis uteri. An appraisal of treatment results for a period of 40 years

A retrospective study was done in 316 patients with primary cervical adenocarcinoma treated at the Research Institute for Clinical and Experimental Oncology in Brno over a period of 40 years (1939-1978). The treatment results were compared to those in 2571 patients with epidermoid carcinomas of the uterine cervix treated at the Institute over the same period. The 5-year survival rate was significantly lower in adenocarcinoma patients (in Stage I patients, 77.8% vs. 84.5%, and, in the whole group, 60.8% vs. 70.3%). The assessment of the treatment results of this study has clearly showed that in cervical adenocarcinomas, surgery combined with radiotherapy was much more effective than radical radiotherapy alone (77.4% vs. 64.7%). In contrast to this, in epidermoid carcinomas the treatment results were better after radical radiotherapy (86.5% vs. 81.3%). Thus, in the prognosis of cervical adenocarcinomas the mass of the tumor, the size of the uterus, as well as the grading play a role. That means that primary cervical adenocarcinomas at early stages can be successfully treated by a combination of radical surgery and radiotherapy, while radiotherapy of advanced stages of this tumor is less successful.     

Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

Table 1     

1-beta-D-arabinofuranosylcytosine-diphosphate-choline is formed by the reversal of cholinephosphotransferase and not via cytidylyltransferase.

In an effort to identify the pathway leading to the formation of 1-beta-D-arabinofuranosylcytosine-diphosphate (ara-CDP)-choline from 1-beta-D-arabinofuranosylcytosine (ara-C) treatment of cultured cells, as well as of cells obtained from leukemia patients, we probed the enzymatic steps involved in the CDP-choline pathway for phosphatidylcholine biosynthesis. Ara-C-triphosphate was not a substrate for CTP:phosphocholine cytidylyltransferase activity under the conditions employed, whereas CTP and dCTP were utilized to form CDP-choline and dCDP-choline, respectively. When presented together, ara-C-triphosphate and CTP inhibited the enzymatic conversion of CTP to CDP-choline in the presence of phosphocholine, with a Ki of 6 mM. Since CTP:phosphocholine cytidylyltransferase did not appear to be responsible for the increased levels of ara-CDP-choline, we next studied the other enzyme in the pathway for phosphatidylcholine synthesis that could form ara-CDP-choline, CDP-choline:1,2-diacylglycerol cholinephosphotransferase. CDP-choline:1,2-diacylglycerol cholinephosphotransferase activity present in microsomes isolated from L5178Y murine leukemia cells exhibited a reversal of its normal catalytic activity, using CMP and 1-beta-D-arabinofuranosylcytosine-monophosphate (ara-CMP) along with phosphatidylcholine to produce either CDP-choline or ara-CDP-choline, plus diradylglycerol. The Vmax and Km values for CMP were 0.78 +/- 0.04 nmol/min/mg and 340 +/- 20 microM, respectively, whereas the Vmax and Km for ara-CMP were 0.22 +/- 0.06 nmol/min/mg and 1410 +/- 540 microM, respectively. A Ki value of 3 mM was obtained for ara-CMP under the cell-free assay conditions used. These results indicate that ara-CDP-choline most likely arises from a reversal of the CDP-choline:1,2-diacylglycerol cholinephosphotransferase utilizing ara-CMP, rather than from the catalysis of ara-C-triphosphate plus phosphocholine to ara-CDP-choline by CTP:phosphocholine cytidylyltransferase. It is speculated that this mechanism may explain, in part, the rapid cellular lysis observed with high dose ara-C therapy.     

Surgical management of major pancreatic injury in children.

INTRODUCTION: Major or complicated pancreatic trauma in children is uncommon and management strategies remain controversial. The aim of this study was to evaluate our experience with both early and delayed surgery in these pediatric cases. METHODS: We carried out a retrospective analysis of data of pediatric patients with major or complicated pancreatic injury operated on between January 1994 and December 2005 in our pediatric trauma center. RESULTS: Thirteen children (9 boys and 4 girls) with a mean age of 8.5 years (range 3 - 16 years) were operated for major or complicated pancreatic injury. The extent of injury was: grade II (major contusion without duct injury or tissue loss) in 4 children; grade III (distal transection) in 5 children and grade IV injury (proximal transection) in four patients. Pseudocyst developed in 8 children: 4 with grade II injury, 2 with grade III injury and 2 with grade IV injury (one with abdominal pseudocyst and one with an abdominal and a mediastinal pseudocyst). Early diagnosis and operation was achieved in 5 cases, while delayed diagnosis and operation occurred in 8. Three children underwent cystogastrostomy; 6 had a spleen-sparing distal pancreatectomy and 4 had resection with Roux-en-Y jejunostomy drainage. Endoscopic retrograde cholangiopancreaticography (ERCP) was the most useful diagnostic tool in assessing ductal injury. There were no deaths or long-term morbidity in our group of patients. CONCLUSIONS: Our results support the view that early operation is important in ductal pancreatic injury. We recommend transferring children with a suspected ductal injury to a tertiary center with experience in both pediatric ERCP and pancreatic surgery.     

A prospective study of tobacco use and multiple myeloma: evidence against an association

The relationship between the use of cigarettes and other tobacco products and the risk of multiple myeloma was examined in a cohort of nearly 250,000 American veterans followed prospectively for 26 years. Compared with men who had never used tobacco, the risk of death from myeloma was not increased among current (relative risk [RR]=0.9, 95 percent confidence interval [CI]=0.8–1.2) or former (RR=1.0, CI=0.8–1.3) cigarette smokers, nor among users of chewing tobacco or snuff (RR=1.0, CI=0.4–2.3). Risk was only slightly and nonsignificantly increased among pipe or cigar smokers (RR=1.2, CI=0.9–1.5). There was no indication of increasing risk with amount of tobacco used or earlier age at first use. With over 90 percent power to detect a 30 percent increased risk of this tumor occuring among current cigarette smokers, this study provides the strongest evidence to date against an association of cigarette smoking with multiple myeloma.Epidemiology and Biometry Program, Division of Cancer Etiology, National Cancer Institute. Westat, Inc. Rockville, MD. National Cancer Institute, 6130 Executive Blvd, Room 418, Rockville, MD 20892, USA.     

Fusion and failure following anterior cervical plating with dynamic or rigid plates: 6-months results of a multi-centric, prospective, randomized, controlled study

Anterior cervical plate fixation is an approved surgical technique for cervical spine stabilization in the presence of anterior cervical instability. Rigid plate design with screws rigidly locked to the plate is widely used and is thought to provide a better fixation for the treated spinal segment than a dynamic design in which the screws may slide when the graft is settling. Recent biomechanical studies showed that dynamic anterior plates provide a better graft loading possibly leading to accelerated spinal fusion with a lower incidence of implant complications. This, however, was investigated in vitro and does not necessarily mean to be the case in vivo, as well. Thus, the two major aspects of this study were to compare the speed of bone fusion and the rate of implant complications using either rigid- or dynamic plates. The study design is prospective, randomized, controlled, and multi-centric, having been approved by respective ethic committees of all participating sites. One hundred and thirty-two patients were included in this study and randomly assigned to one of the two groups, both undergoing routine level-1- or level-2 anterior cervical discectomy with autograft fusion receiving either a dynamic plate with screws being locked in ap - position (ABC, Aesculap, Germany), or a rigid plate (CSLP, Synthes, Switzerland). Segmental mobility and implant complications were compared after 3- and 6 months, respectively. All measurements were performed by an independent radiologist. Mobility results after 6 months were available for 77 patients (43 ABC/34 CSLP). Mean segmental mobility for the ABC group was 1.7 mm at the time of discharge, 1.4 mm after 3 months, and 0.8 mm after 6 months. For the CSLP- group the measurements were 1.0, 1.8, and 1.7 mm, respectively. The differences of mean segmental mobility were statistically significant between both groups after 6 months (P = 0.02). Four patients of the CSLP-group demonstrated surgical hardware complications, whereas no implant complications were observed within the ABC-group (P = 0.0375). Dynamic plate designs provided a faster fusion of the cervical spine compared with rigid plate designs after prior spinal surgery. Moreover, the rate of implant complications was lower within the group of patients receiving a dynamic plate. These interim results refer to a follow-up period of 6 months after prior spinal surgery. Further investigations will be performed 2 years postoperatively.     

A simple cardiac contractility computer

A single-purpose analogue-computing device is described for the online assessment of the contractile state of the human myocardium from the left ventricular pressure (P_lv) data available during routine cardiac catheterisation. Due attention has been paid to the design of the computer circuits so that they will not process pressure phenomena outside the isovolumic contractile period. Either a \(\left( {\frac{1}{{P_{lv} }}\frac{{dP_{lv} }}{{dt}}} \right)_{max} \) or a plain \(\left( {\frac{{dP_{lv} }}{{dt}}} \right)_{max} \) index is presented on a digitalvoltmeter display, thus obviating the need for any graphical extrapolation or additional computation.     

Role of nerve and muscle factors in the development of rat muscle spindles

The soleus muscles of fetal rats were examined by electron microscopy to determine whether the early differentiation of muscle spindles is dependent upon sensory innervation, motor innervation, or both. Simple unencapsulated afferent-muscle contacts were observed on the primary myotubes at 17 and 18 days of gestation. Spindles, encapsulations of muscle fibers innervated by afferents, could be recognized early on day 18 of gestation. The full complement of spindles in the soleus muscle was present at day 19, in the region of the neuromuscular hilum. More afferents innervated spindles at days 18 and 19 of gestation than at subsequent developmental stages, or in adult rats; hence, competition for available myotubes may exist among afferents early in development. Some of the myotubes that gave rise to the first intrafusal (bag₂) fiber had been innervated by skeletomotor (α) axons prior to their incorporation into spindles. However, encapsulated intrafusal fibers received no motor innervation until fusimotor (γ) axons innervated spindles 3 days after the arrival of afferents and formation of spindles, at day 20. The second (bag₁) intrafusal fiber was already formed when γ axons arrived. Thus, the assembly of bag₁ and bag₂ intrafusal fibers occurs in the presence of sensory but not γ motor innervation. However, transient innervation of future bag₂ fibers by α axons suggests that both sensory and α motor neurons may influence the initial stages of bag₂ fiber assembly. The confinement of nascent spindles to a localized region of the developing muscle and the limited number of spindles in developing muscles in spite of an abundance of afferents raise the possibility that afferents interact with a special population of undifferentiated myotubes to form intrafusal fibers.     

Superfluousness of motor innervation for the formation of muscle spindles in neonatal rats

Summary Muscle spindles form de novo in reinnervated muscles of neonatal rats treated with nerve growth factor. Whether the spindles can also form in muscle reinnervated only by afferents was investigated by removing the lumbosacral segment of the spinal cord immediately after crushing the nerve to the medial gastrocnemius muscle at birth, and administering nerve growth factor for 10 days afterwards. As predicted, the medial gastrocnemius muscles were reinnervated by afferents, but not efferents. No motor endplates were visible on any muscle fibers, and extrafusal fibers were atrophied. The reinnervated muscles contained spindle-like encapsulations of one to four fibers at 5, 7, 9 and 30 days after the nerve crush. The number of spindles as well as encapsulated fibers exceeded that of normal medial gastrocnemius muscles. The encapsulated fibers resembled typical intrafusal fibers. They had normal sensory-muscle contacts, but no motor endings. The fibers displayed equatorial clusters of myonuclei and expressed the spindle-specific slow-tonic myosin heavy chain isoform at postnatal day 30. Thus, efferents are not essential for the formation and differentiation of muscle spindles in reinnervated muscles of neonatal rats.