The vasa vasorum and angioplasty

Interruption of flow in the vasa vasorum may lead to medial necrosis and aneurysm formation. The purpose of this study was to determine whether angioplasty produces significant alterations in the morphology or blood flow of the vasa vasorum of the dilated artery. The morphology of the canine vasa vasorum was studied before and after angioplasty; in a separate experiment vessel wall blood flow (VWBF) in canine carotid arteries was measured after angioplasty to determine whether physiologic regulation of the blood flow was disrupted by arterial dilation. No morphologic changes could be demonstrated in the vasa vasorum of the dilated artery; however, VWBF was increased by 1194 +/- 215% (mean +/- standard error, p less than 0.01) between 90 and 120 minutes after angioplasty. VWBF in the adjacent nondilated arterial segment was also increased (720 +/- 177% between 10-30 minutes, p less than 0.01) but returned toward normal after 60 minutes. Adenosine caused a "paradoxical" decrease in VWBF (p less than 0.05) of the dilated arterial segment while causing increased VWBF (p less than 0.05) in the thoracic aorta. Angioplasty appears to produce persistent hyperemia in the dilated arterial wall. A paradoxical response to adenosine suggests that vasa vasorum in the dilated arterial segment are maximally vasodilated. This may be due to mechanical disruption of vasomotor tone or to release of vasoactive substances.     

Detection of Chlamydia trachomatis cervical infection: a comparison of Papanicolaou and immunofluorescent staining in smears obtained by Ayre's spatula and cytobrush.

Two methods of staining (Papanicolaou versus direct immunofluorescence) and two methods of collection of the samples (Ayre's wooden spatula versus cervical Cytobrush) were compared in order to verify the efficiency in detecting Chlamydia trachomatis (CT) infections in the female genital tract. Out of 166 asymptomatic patients, 59 were positive for CT by means of direct immunofluorescence: 36 were detected in Cytobrush samples, 16 in Ayre's spatula samples, and 7 in the samples collected by both methods. Papanicolaou smears showed "moth-eaten" features suggestive of CT infection in a great number of metaplastic cells present in 35 cases: 24 collected by Cytobrush, 4 by Ayre's spatula and 7 by both methods. Our data show that Cytobrush is more efficient that Ayre's spatula in concentrating cellular material. It is thus possible to detect CT infection with more accuracy by means of direct immunofluorescence, and to suspect CT infection in smears collected by means of Cytobrush and stained by Papanicolaou's method.     

Biomechanical analysis of the mechanism of interlocking nail failure

Summary From December 1986 to May 1989, 412 patients with 274 femoral and 144 tibial fractures were treated with Grosse-Kempf interlocking nails at our hospital. 324 cases (78.6%) were followed-up for at least 1 year (average 23 months). There were 13 breakages in the locking nails in femora and none in tibiae. The recorded incidence of breakage in the femur is therefore 4.7% (13/274). The mechanisms of locking nail failure are stress concentration around screw hole and nail slot, nicking of the nail during drilling of the screw holes, too close proximity of the screw hole to the fracture, and larger loading over the proximal femur. The incidence of failure is 4.9% in the upper third, 1.9% in the mid-third, and 8.2% in the distal third (P > 0.05, ² test). The site most at risk is the first screw hole of the distal third, especially if it is near the fracture site. Prevention of failure involves using a nail of larger diameter and sufficient length, improving the surgical drilling technique, and allowing only protected weight bearing. Management of nail breakage by insertion of a new implant and supplementary cancellous bone grafting can gain satisfactory results.     

The compensatory ‘rebound’ of reactive astrogliosis: glial fibrillary acidic protein immunohistochemical analysis of reactive astrogliosis after a puncture wound to the brain of rats with portocaval anastomosis

Summary This study was designed to compare the degree of reactive astrogliosis occurring around a puncture wound in the brain of normal rats and at different intervals after a similar puncture wound in rats with a portocaval anastomosis. The gliosis was evaluated by the number of astrocytes, the thickness of their processes and the intensity of the glial fibrillary acidic protein immunoreactivity. After the puncture wound in the brain of rats with a portocaval anastomosis, the gliosis varied at different intervals being: (1) decreased at 10 days, (2) markedly increased at 5 weeks and (3) significantly decreased at 8, 12, and 16 weeks. These findings suggest that 5 weeks after portocaval anastomosis, an active proliferation of the metabolically altered astrocytes occurs with heightened synthesis of glial fibrillary acidic protein in the period of adaptive compensation, the so-called compensatory rebound. At 8 weeks or more after portocaval anastomosis, these altered astrocytes were considered to be in the phase of decompensation and incapable of maintaining the reactive response which occurred in normal rats. The compensatory rebound and decompensatory decline illustrate the dynamic plasticity of the reactive astrogliosis.Supported by grant from the National Foundation of Natural Sciences No. 386-0956. This paper was read at the XIth International Congress of Neuropathology, September 7, 1990 in Kyoto, Japan     

FLT3-TKD mutation in childhood acute myeloid leukemia.

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. An internal tandem duplication (ITD) of the juxtamembrane domain-coding sequence of the FLT3 gene (FLT3-ITD) is found in 20-25% of adult acute myeloid leukemia (AML) and at a lower frequency in childhood AML. FLT3-ITD is associated with leukocytosis and a poor prognosis, especially in patients with normal karyotype. Recently, there have been three reports on point mutations at codon 835 of the FLT3 gene (D835 mutations) in adult AML. These mutations are located in the activation loop of the second tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD). The clinical and prognostic relevance of the TKD mutations is less clear. To the best of our knowledge, there has been no report to describe FLT3-TKD mutations in childhood AML. In this pediatric series, FLT3-TKD mutations occurred in three of 91 patients (3.3%), an incidence significantly lower than that of FLT3-ITD (14 of 91 patients, 15.4%) in the same cohort of patients. None of them had both FLT3-TKD and FLT3-ITD mutations. Sequence analysis showed one each of D835 Y, D835 V, and D835 H. Of the three patients carrying FLT3-TKD, two had AML-M3 with one each of L- and V-type PML-RARalpha, and another one had AML-M2 with AML1-ETO. None of our patients with FLT3-TKD had leukocytosis at diagnosis. At bone marrow relapse, one of the four patients examined acquired FLT3-ITD mutation and none gained FLT3-TKD mutation.     

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.     

Cell cycle effects of antifolate antimetabolites: implications for cytotoxicity and cytostasis

 Purpose: Cell cycle-related events in CCRF-CEM lymphocytic leukemia cells were examined subsequent to inhibition of thymidylate synthase (TS) or GAR formyltransferase (GARFT) and prior to cell death or stasis. Methods: Cell populations were treated with the GARFT inhibitors 6R-5,10-dideazatetrahydrofolate (lometrexol) or LY309887, the TS inhibitor ZD1694, or the multitargeted antifolate LY231514. DNA content, nucleoside precursor incorporation and proliferating cell nuclear antigen (PCNA) expression as functions of drug treatment were assessed by multiparameter flow cytometry. Cellular respiration was measured by MTT analysis and apoptosis was detected by extraction of DNA fragments. Results: Cell populations treated for up to 96 h with lometrexol or LY309887 did not replicate and maintained a cell cycle distribution with distinct G₁, S and G₂/M regions. The number of S phase cells in treated populations was slightly elevated relative to control as measured by DNA content and PCNA. However, these cells were unable to incorporate 5-bromodeoxyuridine (BrdU). Throughout treatment, cells incubated with GARFT inhibitors maintained intact membranes and respired at a level comparable to untreated cells. In contrast, ZD1694 as well as LY231514, induced synchronization of the treatment population at the G₁/S interface within 12 h of drug addition. This was followed by synchronous entry of the population into S phase. After 24 h of treatment, more than 90% of the cells were capable of incorporating BrdU and stained positive for PCNA. DNA fragmentation occurred in cells treated with ZD1694 or LY231514 but not in those treated with GARFT inhibitors. In addition, the viable cells remaining after 24–48 h of treatment with ZD1694 or LY231514 were respiring at twice the level of untreated cells. Conclusion: These results demonstrate that the distinct endpoints of GARFT and TS inhibition are preceded by distinct cell cycle and metabolic alterations. Received: 1 April 1996 / Accepted: 5 September 1996     

Frequency of bitemporal independent interictal epileptiform discharges in temporal lobe epilepsy

PURPOSE: Bitemporal interictal epileptiform discharges (IEDs) occur in < or =42% of scalp EEGs in patients with temporal lobe epilepsy (TLE) studied with routine EEGs or partial analysis of long-term recordings. METHODS: Twenty-eight patients with TLE demonstrating exclusively unilateral temporal IEDs on routine EEGs underwent 24-h continuous recording. The entire record was visually inspected for epileptiform discharges. We used continuous EEG to assess the significance of long-term recording in detecting bilateral IEDs. RESULTS: Twenty-two patients had left temporal IEDs; 21 had right temporal IEDs. Seventeen (61%) patients had IEDs originating from both the right and left temporal lobes. The probability of detecting bilateral independent IEDs was correlated with the duration of continuous EEG recording. There was no correlation between the number of IEDs originating from one side and the probability of detecting independent IEDs on the other side. The frequencies of IEDs were not correlated with the length of time since onset of epilepsy. CONCLUSIONS: The findings suggest that when long-term recordings are performed, the incidence of bilateral discharges in TLE is higher than previously reported in the literature and supports the view that TLE is commonly a bilateral disease.     

Biomechanical comparison for different configurations of tension band wiring techniques in treating an olecranon fracture

BACKGROUND: The aim of this study was to compare the superiority between the newly designed modified AO tension band wiring technique and the traditional modified AO tension band wiring technique in treating an olecranon fracture. METHODS: Eight pairs of fresh cadaveric ulnae were tested biomechanically. After transverse osteotomy of the olecranon, all left ulnae were fixed by the traditional modified AO technique with two Kirschner wires inserted through the anterior ulnar cortex and all right ulnae by the new technique with two Kirschner wires inserted into the marrow cavity from the olecranon to the ulnar styloid process. All specimens were tested by the Material Testing System machine to evaluate fragment displacement and the maximal failure load. A dual linear variable displacement transducer was used to measure relative minimal displacement. RESULTS: There was no significant difference between the techniques. The maximal failure load by either technique was more than 80 kg. Even at testing failure, no Kirschner wires migrated proximally. CONCLUSION: The new technique may be applied widely to treat all olecranon fractures, because it is a technically easier and safer technique. Less than 5.5-kg loads could be permitted in daily activity postoperatively. A single tolerable loading weight should not exceed 8 kg. Kirschner wires will not migrate proximally, despite increased joint loading. Clinically, this study may confirm indirectly the hypothesis that proximal migration of Kirschner wires was mainly due to triceps traction.