Cerebral mantle thickness: a measurement useful in anatomic diagnosis of fetal ventriculomegaly

The ultrasonographic diagnosis of cerebral ventriculomegaly carries grave implications, in that affected fetuses may suffer abnormal postnatal development or therapeutic abortion. It is important for pathologists to corroborate the clinical diagnosis, but because diagnostic methodologies and criteria differ so radically, this can be problematic. The clinical diagnosis is made primarily by serial ultrasound examinations of the cerebral ventricles, spaces that can be altered postmortem, particularly when the brain is autolysed or deformed artifactually. We therefore sought to learn if examination of tissue, rather than spaces, can identify accurately those fetuses diagnosed with cerebral ventriculomegaly by prenatal ultrasound. The thickness of the cerebral mantle was obtained in 100 control fetuses aged 14 to 26 postmenstrual weeks. Statistical analysis revealed significant correlation of cerebral mantle thickness with crown-rump length, foot length, and head circumference. Twenty fetuses diagnosed with ventriculomegaly showed mantle thicknesses that were less than the control mean. In a few cases, mantle thickness fell between the mean and -1 SD; in several others, thickness was diminished by -1 SD to -2 SD; in one-half of cases, mantle thickness was 2 SDs or more below the expected mean. Head circumference was within 2 SDs of the control mean in most cases, and increased beyond 2 SDs in only two cases. Head circumference is an unreliable indicator of ventriculomegaly in the midgestational fetus. By contrast, cerebral mantle thickness is a simple and useful way of corroborating ultrasonographic diagnoses at autopsy and may also prove useful in clinical settings.     

Role of maintenance treatment in opioid dependence

Methadone maintenance treatment (MMT) involves the daily administration of the oral opioid agonist methadone as a treatment for opioid dependence-a persistent disorder with a substantial risk of premature death. MMT improves health and reduces illicit heroin use, infectious-disease transmission, and overdose death. However, its effectiveness is compromised if low maintenance doses of methadone (<60 mg) are used and patients are pressured to become prematurely abstinent from methadone. Pregnancy and psychiatric comorbidity are not contraindications for MMT. As an alternative to MMT, other oral opioid agents (eg, naltrexone, buprenorphine) may increase patient choice and avoid some of the more unpleasant aspects of MMT. The public-health challenge for the future is to develop and continue to deliver safe and effective forms of opioid maintenance treatment to as many opioid-dependent individuals as can benefit from them.     

The aminoacceptor stem of the yeast tRNA(Lys) contains determinants of mitochondrial import selectivity

The effect of quinine, a cinchona alkaloid, was studied on gastrointestinal transit in mice. Intraperitoneal (i.p.) administration of quinine inhibited the intestinal propulsion of a charcoal suspension at a dose of 100 mg/kg, comparing favorably with 5 mg/kg morphine. In an attempt to probe into the mechanism underlying this inhibition, a possible modulation by minoxidil (1 mg/kg, p.o.) and glibenclamide (1 mg/kg, p.o.), the drugs that, respectively, open and close ATP-sensitive K+ channels was tested on gastrointestinal transit in animals treated or not with quinine or morphine. While minoxidil produced no significant change of normal transit, glibenclamide significantly increased it. However, both drugs blocked the quinine-induced reduction in gastrointestinal transit. In contrast, the inhibitory effect of morphine on gastrointestinal transit was not modified by either drug. The effects of quinine as well as of morphine on gastrointestinal transit were significantly antagonized by naloxone (2 mg/kg, s.c.), a mu-opioid receptor antagonist but not by yohimbine (1 mg/kg, i.p.), an alpha2-adrenoceptor antagonist. Furthermore, quinine at a lower dose (25 mg/kg) that showed no per se effect on gastrointestinal transit, significantly potentiated the response to 2.5 mg/kg morphine. Although the role of ATP-sensitive K+ channels in the action of quinine and morphine was not clarified by the present results, a possible involvement of endogenous opioid(s) in the quinine-induced inhibition of gastrointestinal transit can be suggested.     

The effect of post-injury spinal position on canal occlusion in a cervical spine burst fracture model

STUDY DESIGN: The canal space of burst-fractured, human cervical spine specimens was monitored to determine the extent to which spinal position affected post-injury occlusion. OBJECTIVE: To test the null hypothesis that there is no difference in spinal canal occlusion as a function of spinal positioning for a burst-fractured cervical spine model. SUMMARY OF BACKGROUND DATA: Although previous studies have documented the effect of spinal positioning on canal geometry in intact cadaver spines, to the authors' knowledge, none has examined this relationship specifically in a burst fracture model. METHODS: Eight human cervical spine specimens (levels C1 to T3) were fractured by axial impact, and the resulting burst injuries were documented using post-injury radiographs and computed tomography scans. Canal occlusion was measured using a custom transducer in which water was circulated through a section of flexible tygon tubing that was passed through the spinal canal. Any impingement on the tubing produced a rise in fluid pressure that was monitored with a pressure transducer. Each spine was positioned in flexion, extension, lateral (and off-axis) bending, axial rotation, traction, and compression, while canal occlusion and angular position were monitored. Occlusion values for each position were compared with measurements taken with the spine in neutral position. RESULTS: Compared with neutral position, compression, extension, and extension combined with lateral bending significantly increased canal occlusion, whereas flexion decreased the extent of occlusion. In extension, the observed mechanism of occlusion was ligamentum flavum bulge caused by ligament laxity resulting from reduced vertebral body height. CONCLUSIONS: Increased compression of the spinal cord after injury may lead to more extensive neurologic loss. This study demonstrated that placing a burst-fractured cervical spine into either extension or compression significantly increased canal occlusion as compared with occlusion in a neutral position.     

Bone marrow transplantation for severe aplastic anemia: has outcome improved?

Bone marrow transplants for severe aplastic anemia were first performed in the 1970s. Transplant regimens, supportive care, and patient selection have changed substantially since then. Our objective was to determine the impact of these changes on transplant outcome. We studied 1,305 recipients of HLA-identical sibling transplants for aplastic anemia between 1976 and 1992, reported to the IBMTR by 179 centers. We compared survival of transplants performed in three intervals (1976 through 1980 [n = 186], 1981 through 1987 [n = 648], and 1988 through 1992 [n = 471]) using Cox proportional hazards regression. Five-year survival (+/-95% confidence interval) increased from 48% +/- 7% in the 1976-1980 cohort to 66% +/- 6% in the 1988-1992 cohort (P < .0001). Risks of graft-versus-host disease (GVHD) and interstitial pneumonia decreased over time, but the risk of graft failure did not. Higher long-term survival resulted primarily from decreased mortality in the first 3 months posttransplantation. Late mortality risks were low and changed little over the intervals studied. In multivariate analysis, changes in transplantation strategies accounted for most but not all of the improved outcome. Use of cyclosporine to prevent GVHD was the most important factor. Changes in patient selection did not seem to explain improved survival. Survival after HLA-identical sibling bone marrow transplantations for aplastic anemia has improved since 1976. Changes in GVHD prophylaxis account for much of this improvement. Other changes may also operate.     

DNA repair: caretakers of the genome?

Recent results show that the 8-oxoguanine DNA repair system is functionally conserved in bacteria and mammals. The bacterial system protects the genome from the mutagenic effects of oxidative stress; the role of the mammalian system is expected to be similar and defects in it may increase susceptibility to cancer.     

Primary chemotherapy for stage 2 testis cancer

To evaluate the efficacy and toxicity of primary chemotherapy in patients with stage 2 (retroperitoneal lymph node metastases) testis cancer, 20 consecutive patients referred to Groote Schuur Hospital between September 1992 and March 1994 were reviewed. There were 10 patients with non-bulky non-seminomatous germ cell tumour (NSGCT), 5 with bulky NSGCT and 5 with bulky seminoma. The treatment regimen consisted initially of 4 cycles of cisplatin, etoposide and bleomycin. Patients with NSGCT and a residual mass after chemotherapy subsequently underwent retroperitoneal lymph node dissection (RPLND) and those with seminoma underwent a low dose of irradiation to the mass. In 7 (70%) of the 10 patients with non-bulky NSGCT, there was a complete response to chemotherapy and 3 patients underwent limited RPLND. One patient relapsed at follow-up but remains clear of disease after salvage therapy. The survival rate is 100% at a median follow-up of 60 months (range 12-143 months). In 5 patients with bulky NSGCT there was no complete response to chemotherapy. Three have undergone limited RPLND. The survival rate is 52% at a median follow-up of 130 months (range 108-152 months). In 5 patients with bulky seminomas, the survival rate is 100% at a median follow-up of 55 months (range 29-92 months). Toxicity has been modest except for 1 patient who died postoperatively in the early part of the study. Four patients have fathered children after treatment. We conclude that primary chemotherapy is the treatment of choice for patients with stage 2 testis cancer.