Sequelae of lateral ovarian transposition in irradiated cervical cancer patients

Lateral ovarian transposition (LOT) is a useful technique for preserving ovarian function in "high-risk" premenopausal Stage I cervix cancer patients who undergo hysterectomy and subsequent postoperative whole pelvic radiation therapy. From 1978 to 1988, 38 FIGO Stage I cervical cancer patients underwent LOT as part of their initial operative procedure and 14 of these patients (37%) subsequently received pelvic radiation therapy (LOT + RT) because of pathological findings such as metastatic pelvic lymph node involvement or positive surgical margins (13 patients) or recurrent disease (1 patient). Ten (71%) of the 14 (LOT + RT) patients have maintained ovarian function with a median follow-up of 35 months. Preservation of ovarian function was directly related to the estimated scatter dose to the ovaries. For patients whose estimated ovarian dose was 300 cGy or less, only 1 of 9 patients (11%) underwent menopause, whereas 3 of 5 patients (60%) became menopausal if the ovarian dose was more than 300 cGy. The placement of the ovaries was also crucial for preservation of ovarian function, with 100% of the patients developing menopause if the ovaries were placed below the iliac crest. A major side effect of LOT was the development of symptomatic ovarian cysts in 7 (18%) of the 38 Stage I patients who underwent LOT. In the 24 patients who underwent LOT alone without RT, the incidence of symptomatic ovarian cysts was 25% compared to only 7% of the patients who underwent LOT + RT, although this difference was not statistically significant (p = .18).     

The cause and incidence of secondary insults in severely head-injured adults and children

The cause and incidence of reductions in cerebral perfusion pressure, and rises in intracranial pressure have been examined in a series of patients with severe head injury defined as an initial Glasgow Coma Sum of less than or equal to 8. Two-hundred-and-seven adults (aged over 16 years) and 84 children admitted to Newcastle General Hospital, who had intracranial pressure monitoring as part of their routine management, were studied. Intracranial pressure (ICP), arterial pressure and cerebral perfusion pressure (CPP) were sampled and recorded every 2 min. Patients' CT findings were classified into distinct groups using the method described by Marshall. Secondary insults were defined using the Edinburgh University Secondary Insult Grades (EUSIG) and the incidence and cause (raised ICP, reduced CPP or a combination of the two) was established. Outcome was assessed at 6 months using the Glasgow Outcome Scale. In the majority of adults with head injury it is the combination of reduced arterial pressure and raised ICP that contributes to the reduction in cerebral perfusion pressure. This was not the case for Diffuse Injury Type I. In children similar characteristics were found across each of the CT classifications. The vast majority of falls in CPP down to 60 mmHg were caused by reduced arterial pressure. Reductions below 50 mmHg were almost always due to a combination of both reduced arterial pressure and raised ICP. The results in adults were similar, but not identical, to those of the paediatric cases. Diffuse Injury Type I stood out from all the other categories as the only one where reductions in perfusion pressure were almost exclusively due to reductions in arterial pressure and not to increases in ICP. The management of these patients should ensure the adequacy of perfusion pressure by maintaining arterial pressure at a satisfactory level. These results suggest that vigilant monitoring of both intracranial pressure and arterial pressure is required to lower the incidence of secondary insults.     

Successful treatment with lamivudine for fulminant reactivated hepatitis B infection following intensive therapy for high-grade non-Hodgkin's lymphoma

Chronic carriers of Hepatitis B virus (HBV) infection, who are treated for malignant lymphoma, are at high risk of mortality from reactivated HBV infection. We report a case of a 29-year-old male chronic HBV carrier who developed fulminant reactivated HBV infection following intensive chemotherapy for stage IV^B large cell B-cell non-Hodgkin's lymphoma associated with extensive central nervous system and bone marrow involvement. Prior to chemotherapy the patient had normal liver function tests and was negative for HBV DNA by semi-quantitative PCR assay. Fulminant HBV reactivation was confirmed following clinical deterioration, massive rises in hepatic transaminases (peak alanine aminotransferase = 2,850 U/l), liver biopsy and rising levels of serum HBV DNA. Following treatment with lamivudine 150 mg bd for 18 weeks dramatic and sustained recovery ensued. Symptoms and liver function tests improved within days and HBV DNA became negative within 12 weeks. Our patient later died from relapsed lymphoma but without evidence of reactivated HBV infection. We advise that lamivudine should be considered during intensive chemotherapy treatment of chronic carriers of HBV.     

Antiparkinsonian actions of CP-101,606, an antagonist of NR2B subunit-containing N-methyl-d-aspartate receptors

In the setting of nigrostriatal dopamine depletion, glutamatergic pathways to the striatum and basal ganglia output nuclei become overactive. Systemically administered glutamate receptor antagonists may have direct antiparkinsonian actions in rodents, but there is little evidence for this in primates. Glutamate antagonists may also potentiate conventional dopaminergic therapies; however, there is concern that broad spectrum, nonselective antagonists may have unwanted side-effects. Because subunit-selective antagonists may avoid these liabilities, we have examined the antiparkinsonian effects of a selective antagonist of the NR2B subunit of the NMDA receptor. In rats, CP-101,606 decreased haloperidol-induced catalepsy with an ED(50) of about 0.5 mg/kg. In MPTP-treated monkeys, CP-101,606 (1 mg/kg) reduced parkinsonian motor symptoms by 20%. At a dose of 0.05 mg/kg, CP-101,606 markedly potentiated the effect of a submaximal dose of levodopa, reducing motor symptoms by about 50% compared to vehicle and by about 30% compared to levodopa alone. No side-effects were apparent at any dose of CP-101,606. We conclude that CP-101,606 has direct antiparkinsonian actions in both rodents and monkeys and it synergistically potentiates levodopa in MPTP-treated monkeys. Clinical evaluation of selective NR2B antagonists may be warranted in Parkinson's disease.     

Immunohistochemical localization of the P2Y1 purinergic receptor in Alzheimer's disease

The biological actions of extracellular nucleotides are mediated by two distinct classes of P2 receptor, P2X and P2Y. The G protein-coupled P2Y receptors comprise five mammalian subtypes, P2Y(1-11). The P2Y1 subtype is expressed abundantly throughout the human brain and is specifically localized to neuronal structures. In the present study, the distribution of the P2Y1 receptor was investigated in Alzheimer's disease (AD) brains. In contrast to control human brain, the P2Y1 receptor was localized to a number of characteristic AD structures such as neurofibrillary tangles, neuritic plaques and neuropil threads. Immunoblot analysis showed that this specific immunostaining observed over tangles was not a result of cross-reactivity between the anti-P2Y1 antiserum and abnormal tau protein, the major constituent of tangles. The significance of this altered P2Y1 cellular distribution in AD brains is at present unclear.     

Ischemic preconditioning enhances recovery of isolated rat lungs after hypothermic preservation

BACKGROUND: Ischemic preconditioning, an endogenous protection mechanism, occurs in many organs, including lungs. The efficacies of differing ischemic durations in protecting the lung are unknown. We compared the ability of three preconditioning protocols to protect rat lungs during storage. METHODS: Function was measured in five groups of perfused, ventilated rat lungs. Group 1 lungs underwent control perfusion (60 minutes) without storage. Groups 2 through 5 underwent the following prestorage protocols: group 2, 20 minutes of perfusion; group 3, 10 minutes of perfusion, 5 minutes of cessation of ventilation and perfusion (ischemia), and 5 minutes of reperfusion; group 4, 5 minutes of perfusion, 10 minutes of ischemia, and 5 minutes of reperfusion; and group 5, 2 periods of 5 minutes of ischemia and 5 minutes of reperfusion. Lungs were then flushed with, and immersed (6 hours) in modified bicarbonate buffer (4 degrees C). Lung function was reassessed during 40 minutes of reperfusion (37 degrees C). Subsequently we examined preconditioning by stopping ventilation or perfusion separately. RESULTS: After reperfusion, lungs in group 2 had a compliance of 0.015+/-0.002 mL/cm H2O (mean +/- SE, n = 10), significantly lower than lungs in group 1 (0.063+/-0.002 mL/cm H2O). Ischemic preconditioning was protective, with lungs in groups 3, 4, and 5 having compliances greater (p<0.05) than those in group 2. Preconditioning by cessation of ventilation alone was also effective. CONCLUSIONS: Preconditioning attenuates deterioration in lung compliance on reperfusion to a degree dependent on the protocol used.