Involvement of pre- and postsynaptic NMDA receptors at local circuit interneuron connections in rat neocortex.

To investigate the involvement of N-Methyl-D-aspartate (NMDA) receptors in local neocortical synaptic transmission, dual whole-cell recordings - combined with biocytin labelling - were obtained from bitufted adapting, multipolar adapting or multipolar non-adapting interneurons and pyramidal cells in layers II-V of rat (postnatal days 17-22) sensorimotor cortex. The voltage dependency of the amplitude of Excitatory postsynaptic potentials (EPSPs) received by the three types of interneuron appeared to coincide with the interneuron subclass; upon depolarisation, EPSPs received by multipolar non-adapting interneurons either decreased in amplitude or appeared insensitive, multipolar adapting interneuron EPSP amplitudes increased or appeared insensitive, whereas bitufted interneuron EPSP amplitudes increased or decreased. Connections were challenged with the NMDA receptor antagonist d-(-)-2-amino-5-phosphonopentanoic acid (d-AP5) (50µM) revealing NMDA receptors to contribute to EPSPs received by all cell types, this also abolished the non-conventional voltage dependency. Reciprocal connections were frequent between pyramidal cells and multipolar interneurons, and inhibitory postsynaptic potentials (IPSPs) elicited in pyramidal cells by both multipolar adapting and multipolar non-adapting interneurons were sensitive to a significant reduction in amplitude by d-AP5. The involvement of presynaptic NMDA receptors was indicated by coefficient of variation analysis and an increase in the failures of transmission. Furthermore, by loading MK-801 into the pre- or postsynaptic neurons, we observed that a reduction in inhibition requires presynaptic and not postsynaptic NMDA receptors. These results suggest that NMDA receptors possess pre- and postsynaptic roles at selective neocortical synapses that are probably important in governing spike-timing and information flow.

Evaluating the third and fourth derivatives of spectral data.

The problem of differentiating spectral data to yield the third and fourth derivatives is converted into one of solving an integral equation of the first kind. This equation is solved by Tikhonov regularization. The method of General Cross Validation is used to guide the choice of the regularization parameter that keeps noise amplification under control. The performance of this route to third and fourth derivative spectra is demonstrated by applying it to a number of published spectra. A computational problem associated with General Cross Validation has been identified.

Nightly enteral nutrition support of elderly hip fracture patients: a phase I trial.

OBJECTIVE: This non-blinded randomized controlled trial was the first phase of a planned series of investigations designed to test the efficacy of aggressive post-operative enteral nutrition support to decrease the rate of post-operative complications or improve long-term outcomes in specifically defined subgroups of elderly patients who have sustained a hip fracture requiring surgery. METHODS: Eighteen patients (17 males) were randomized to the treatment (eight male subjects) or control groups. The control group (mean age 76.5+/-6.1 years) received standard post-operative care. Subjects in the treatment group (mean age 74.5+/-2.1 years) received 125 cc/hour of nasoenteral tube feedings over 11 hours each night in addition to standard post-operative nutritional care. RESULTS: Both the treatment and control groups had reduced volitional nutrient intakes for the first 7 post-operative days (3,966+/-2,238 vs. 4,263+/-2,916 kJ/day [948+/-535 vs. 1019+/-697 kcal/day], p=0.815), but the treatment subjects had a greater total nutrient intake (7,719+/-2,109 vs. 4,301+/-2,858 kJ/day [1845+/-504 vs. 1028+/-683 kcal], p=0.012). On average, treatment subjects were tube fed for 15.8+/-16.4 days. There was no difference between the groups (treatment vs. controls) in the rate of post-operative life-threatening complications (25 vs. 30%, p=1.00) or in-hospital mortality (0 vs. 30%, p=0.216). Mortality within 6 months subsequent to surgery was lower in the treatment group compared to the controls (0 vs. 50%, p=0.036). DISCUSSION: We conclude that nightly enteral feedings are a safe and effective means of supplementing nutrient intake. The greatest impact of nutrition support may be to reduce mortality.

The change in serum protein concentration in response to the stress of total joint surgery: a comparison of older versus younger patients.

OBJECTIVE: To investigate whether the physiological response to surgery-induced stress, as measured by changes in serum secretory proteins, is more profound on older than in younger total joint arthroplasty patients. DESIGN: Retrospective study. SETTING: A 267-bed teaching hospital. PARTICIPANTS: A total of 220 ambulatory patients with normal admission serum albumin levels, of whom 106 were 65 years of age or older (mean age 73.3 +/- 6.2 years) and 114 less than age 65 (mean age 48.8 +/- 12.2 years). METHODS: Serum albumin and transferrin levels obtained at admission an on the fifth and tenth postoperative days were compared in the two age groups. RESULTS: In both age groups, admission serum albumins were significantly higher than on the corresponding postoperative Day 5 levels (40.4 +/- 3.7 g/L vs 25.0 +/- 3.3 g/L, P < .0001 and 39.5 +/- 2.5 g/L vs 23.9 +/- 3.1 g/L, P < .001 in older and younger patients, respectively). The drop in the serum concentration of albumin by postoperative Day 5 in the older patients was not significantly different from that of the younger patients (a drop of 15.6 +/- 3.3 g/L in older vs 15.4 +/- 4.4 g/L for the younger, P = .740). Among the 64 patients who remained in the hospital 10 days subsequent to surgery, the average postoperative Day 10 serum albumin concentration was significantly lower in the older patients when compared with the younger (26.2 vs 29.1 g/L P = .016). Similar results were obtained for serum transferrin. CONCLUSIONS: Subsequent to elective arthroplasty, the magnitude of change in serum albumin and transferrin concentrations is similar in older compared with younger, patients, suggesting that this stress response to surgery is nor age dependent. In contrast, the rate of recovery of the serum protein concentrations to preoperative levels may be slower in the older patients. However, this issue needs to be investigated further.

Effect of delayed admission to the hospital on the preoperative prevalence of deep-vein thrombosis associated with fractures about the hip.

Thirteen (10 per cent) of 133 patients who had venography on admission to the hospital for a fracture about the hip had radiographic evidence of deep-vein thrombosis. Only seven (6 per cent) of the 122 patients who were seen at the hospital within two days after the fracture had evidence of thrombosis. However, six of the eleven patients who had a delay of more than two days between the fracture and admission to the hospital had evidence of thrombosis. Although there was no significant difference between these two groups with respect to the mean age, sex distribution, frequency of fracture type, or history of deep-vein thrombosis, there was a significant difference in the prevalence of thrombosis in the patients who had a delay before admission to the hospital compared with those who did not (p<0.001). These results suggest that there is a substantial risk of venous thromboembolic disease in patients who have a fracture about the hip, regardless of whether or not they have had an operation, and that this risk increases if the time to presentation is delayed. Consequently, patients for whom there was a delay between a fracture about the hip and admission to the hospital should be considered to be at high risk for, and should be evaluated for, deep-vein thrombosis preoperatively.

Infective endocarditis in a collegiate wrestler.

A 21-year-old collegiate wrestler was admitted to the hospital suffering from acute left lower quadrant abdominal pain. Blood cultures taken at the time of admission showed Staphylococcus aureus. The results of a computed tomography scan and a two-dimensional echocardiogram were consistent with a diagnosis of infective endocarditis. Therapy consisted of a 14-day hospitalization, a 28-day course of parenteral antibiotics, and subsequent follow-up visits. He returned to full participation in wrestling after 15 weeks.

Inhibition of lymphocyte protein kinase C by unsaturated fatty acids.

Oleic, arachidonic, eicosapentaenoic and docosahexaenoic acids inhibited lymphocyte protein kinase C activity in the presence of Ca2+, phospholipid and a phorbol ester. Linoleic and alpha-linolenic acids did not affect protein kinase C activity in this way and none of the fatty acids affected protein kinase A activity. These findings indicate direct inhibitory effects of some unsaturated fatty acids upon protein kinase C. Culture of lymphocytes in the presence of oleic, arachidonic, eicosapentaenoic or docosahexaenoic acids resulted in a reduction in protein kinase C activity (by up to 45%). Culture with linoleic or alpha-linolenic acids did not affect protein kinase C activity and none of the fatty acids affected total protein kinase A activity or the percentage in the active form. These results show for the first time that fatty acids have long term effects upon protein kinase C activity, perhaps as a result of altering the rate of turnover of the enzyme. It is suggested that the inhibition of lymphocyte functions caused by unsaturated fatty acids may in part be due to their effect on protein kinase C.

Risk factors and 10-year breast cancer survival in northern Alberta.

1,121 women in northern Alberta diagnosed as having breast cancer between 1971-74 were followed for 10 years. Risk factors for breast cancer were studied with respect to their possible influence on survival by comparing survival curves, using both Logrank and Cox's regression model, and controlling for intercurrent death, stage and axillary node status. A complex interaction was found between age and menopausal status and survival rates. Premenopausal women aged 45-55 had a better survival rate than postmenopausal women of the same age. However, one subgroup of premenopausal women aged 35-39 had a significantly worse prognosis than those aged 40-44 as did a group of post menopausal women aged 70-74. No cause was found other than the effect of age. There was a significant trend to worsening survival with heavier weight at time of diagnosis and with breast feeding. Parity of five or more and family history of breast cancer were less consistently associated with worse survival. Oral contraceptive use was only associated with worsened prognosis significantly when stage was controlled for; there was no overall effect. Age at menarche and age at first birth did not influence prognosis. Theories to explain the findings are discussed.

PIP: Risk factors associated with 10-year survival with breast cancer were analyzed using survival curves, with both Log rank and Cox's regression models, controlling for intercurrent death, stage and axillary node status. 1121 women from northern Alberta diagnoses with breast cancer from 1971-1974 were followed for 10 years, with history and physical exams done on 92% of patients by 1 or 2 persons. At 10 years only 41 were lost to follow-up, 41% were alive and well, 10% were alive with metastatic disease, 34% were dead from breast cancer and 11% were dead from other causes. Premenopausal women aged 45-55 had better survival than postmenopausal women of the same age. Premenopausal women aged 35- 59 had a significantly worse prognosis than women aged 40-44. Women aged 70-74 also had a poor prognosis. Worse survival was associated with heavier weight at diagnosis. Women with history of breast feeding for 2 weeks or more had a 51% survival rate, less than the 60% for those who did not breast feed. Parity of 5 or higher and family history of breast cancer were less closely related to worse survival. Oral contraceptive use 1 month or more had no overall association, but was associated with worse prognosis when stage was controlled. Age at menarche and age at 1st birth did not influence prognosis.

The behavior of the expanding point .25 ACP ammunition in the human body.

We examined six cases (four homicides, two suicides) involving gunshot wounds with .25 ACP ammunition. The nature of these cases is described in this article.

Reproductive events and family history as risk factors for breast cancer in northern Alberta.

Reproductive events and family history as risk factors for breast cancer in northern Alberta were investigated with the use of data from a computerized population-based registry. Women aged 30 to 79 years attending diagnostic breast clinics at the Cross Cancer Institute from 1971 through 1975 constituted the two study groups; 1232 women had diagnosed breast cancer (malignant disease group) and 602 women were clinically free of all types of breast disease (control group). An increased relative risk of breast cancer was found in women with a family history of breast cancer, those who gave birth to their first term infant at age 30 years or older, those in whom more than 15 years elapsed between menarche and that birth, and those with a late natural menopause. There was a decreased risk, relative to nulliparity, in the postmenopausal women who first gave birth to a term infant 5 years or less after menarche. Artificial menopause (bilateral oophorectomy), parity and age at menarche had no apparent effect on the risk. The pattern of risk factors in northern Alberta differed from that reported for other geographic areas, including other provinces of Canada, thus emphasizing the need for local studies in the planning of screening programs.