PREPARTUM DEPRESSION—A Study of Seventy Unwed Mothers Treated with d-Amphetamine Sulfate and Amobarbital

Seventy unwed pregnant patients in states of mild to moderate depression evidenced by one or more symptoms (tenseness, “nervousness,” crying spells, listlessness, fatigue, nausea and vomiting, insomnia and overeating), received informal psychotherapy and a sustained-release capsule combining d-amphetamine sulfate and amobarbital.Forty-eight patients had complete or substantial relief of symptoms, 15 had partial relief, seven had slight or no relief.Use of the preparation seemed to make tense, “nervous” patients more communicative and amenable to counseling, but was less effective in listless, easily fatigued patients.Because of its direct mood-alleviating action and its ability to facilitate psychotherapy, the d-amphetamine sulfate-amobarbital combination proved a very effective treatment for mild and moderate depression accompanying pregnancy.     

Pharmacokinetics of imipramine are affected by age and sex in rats

Chronic treatment with the antidepressant imipramine (IMI) leads to accumulation of imipramine's major metabolite desmethylimipramine (DMI) in the brain. Juvenile, young and middle-aged female rats, as well as juvenile and young male rats were treated chronically with imipramine (14 days) and analyzed 24 hours later for levels of IMI and DMI in the hypothalamus-preoptic area (HPA) and serum. Older animals of both sexes showed higher levels of DMI than juvenile animals, in both the HPA and serum. Females also had higher DMI levels than males at comparable ages. Analysis of IMI and DMI levels at intervals after a single imipramine injection suggested that the initial metabolism of imipramine is slower in older animals and in females (compared to males). The results indicate that age and gender alter the initial metabolism of imipramine, leading to enhanced accumulation of metabolites during chronic treatment in older animals and in female rats, compared to younger rats and males, respectively.     

Interactions between Sympathomimetic Amines and Antidepressant Agents in Man

Intravenous infusions of phenylephrine, noradrenaline, adrenaline, and isoprenaline were given to healthy human volunteers after five to seven days on phenelzine, tranylcypromine, or imipramine, and cardiovascular responses were compared with those observed under control conditions. With monoamine oxidase inhibitors there was a 2-2½ fold potentiation of the pressor effect of phenylephrine, but no clinically significant potentiation of cardiovascular effects of noradrenaline, adrenaline, or isoprenaline. With imipramine there was potentiation of the pressor effects of phenylephrine (2-3 fold), noradrenaline (4-8 fold), and adrenaline (2-4 fold); there were dysrhythmias during adrenaline infusions, but no noticeable or consistent changes in response to isoprenaline.Noradrenaline and adrenaline in amounts contained in local anaesthetics used in dentistry are not likely to be significantly potentiated in otherwise healthy patients receiving monoamine oxidase inhibitors. Hazardous potentiation of their cardiovascular effects might occur in patients receiving tricyclic antidepressants.Our observations do not indicate that the hazards associated with isoprenaline inhalation by bronchial asthmatics would be increased by coincident therapy with a monoamine oxidase inhibitor or tricyclic antidepressant.     

Myocardial Infarction and Carbohydrate Metabolism Relating to Diabetes Mellitus

Fifteen non-obese males with acute myocardial infarction and no diabetic history were evaluated for diabetes. During infarction, results of oral glucose tolerance tests were “diabetic” or “probably diabetic” in 10 of the 15 patients (67 percent). The plasma immuno-reactive insulin response in 12 patients (80 percent) was of a pattern observed in patients with maturity-onset diabetes. Six months after infarction, follow-up glucose tolerance tests in 12 surviving patients were diabetic or probably diabetic in three cases (25 percent). In seven of twelve patients (58 percent) had delay in the peaking of the plasma insulin response to an oral glucose tolerance test, a phenomenon that is observed in patients with maturity-onset diabetes.Glucose tolerance tests were abnormal in one of fourteen control subjects (7 percent). There was a delayed plasma insulin response to an oral glucose test in two of fourteen controls (14 percent).Patients with myocardial infarction have an increased incidence of diabetes mellitus.     

A NEW ANTIHYPERTENSIVE AGENT—Clinical Evaluation of a Rauwolfia-Flumethiazide Combination (Rautrax?)

Twenty-eight patients were treated with Rautrax,® a combination of flumethiazide, rauwolfia and potassium chloride for from one to seven months. The average mean blood pressure for the group declined from 135 mm. of mercury to 107 mm. All but two of the patients had a decrease in blood pressure and 19 became normotensive. Associated symptoms of headache, dyspnea, edema and angina were completely relieved or improved in the majority of patients with these complaints. On the basis of the blood pressure response and the clinical effects seen in the patient, therapeutic results were classified as good to excellent in 22 of the 28 patients, fair in two, and poor in three. No evaluation was made in the remaining patient in the series because further adjustment in dosage was required.Three patients had side effects—moderate gastrointestinal upset in one case, headache and a sensation of the bladder''s having been “wrung out” in another, and headache and paresthesia of the legs in the third. Only the third patient had persisting symptoms after the drug was discontinued. In the other two reduction of dosage sufficed.     

Onset,Early Stages,and Prognosis of Rheumatoid Arthritis: A Clinical Study of 100 Patients with 11-year Follow-up

One hundred patients with “definite” or “classical” rheumatoid arthritis were followed in a hospital clinic from within one year of the onset of the arthritis. The average interval between onset and first attendance was 3·7 months. Onset was commoner in the winter, transient prodromal symptoms being noted in 23, with possible precipitating factors in 14. The serum rheumatoid factor test was positive at some time in 88.The patients were reassessed between eight and 14 years later. Seventeen died during this period, five possibly as a result of the disease or its treatment.The remaining patients had improved as a whole in terms of the blood sedimentation rate, haemoglobin, titre of the rheumatoid factor test, and status of the disease, but there was an overall deterioration in functional capacity. Both the rheumatoid factor titre and the functional capacity at an earlier review could be directly correlated with the outcome, but other factors were not found to influence the ultimate prognosis.     

Weight Increase of Cotton Fibers During Swelling in Alkali as a Sensitive Measure of Cellulose Degradation in Ruminal Fluid

Weight increase of cotton fiber in an 18% NaOH solution, termed “alkali-centrifuge” or “AC” value, was measured after incubation of either 1 g or 100 mg of the fiber in ruminal fluid. The AC response was a sensitive measure of cellulolytic activity. Thus, fiber incubated at 21 and 51°C exhibited major AC increases even when direct weight losses of the unswollen fiber were less than 2%. Similarly, progressive additions of acetic acid to ruminal fluid progressively depressed both AC response and direct weight loss, but the former was still easily measurable when the latter was not. In tightly closed, completely filled vials with high ratio of ruminal fluid to sample, AC increased greatly and rapidly, i.e., in 6 h. This time could be further reduced to 2 h by overnight “preincubation” of the ruminal fluid with cotton fiber before starting the test incubation. Certain surfactants used to aid wetting of the fiber had a low but measurable potency in inhibiting cellulose digestion, but other surfactants were non-inhibitory. The AC response was maintained when ruminal fluid was diluted with an equal amount of McDougall's “artificial saliva” solution.     

Benign Intracranial Hypertension following Corticosteroid Withdrawal in Childhood

In an 18-month period seven children who were treated for a variety of neurological and non-neurological diseases, and in whom the corticosteroid or corticotrophin dosage was reduced, developed a syndrome indistinguishable from “benign intracranial hypertension.” The total duration and rate of reduction of corticosteroid dosage and perhaps an underlying susceptibility to cerebral oedema appear to be important factors in this syndrome. Usually patients can be treated without the need for special neuroradiological studies. Possibly mild forms of this condition are not uncommon, but its pathogenesis is still uncertain.     

The frequency of genetic disease and congenital malformation among patients in a pediatric hospital

A sample of 12,801 admissions to a pediatric hospital was surveyed in 1969-70 to determine the prevalence of disease which could be classified as “genetic” in origin or related to “congenital malformation”.“Genetic” admissions accounted for 11.1% of the total while 18.5% were for congenital malformations; about 2% (unknown group) were probably genetic. Therefore about one third of all admissions represent the effect of abnormal gene-environment interrelations at some point in the development or life of the patient.The “genetic” patient is admitted more often to a medical service while the patient with congenital malformation usually goes to a surgical service; the former stays 7.3 days and the latter 8.6 days. A disproportionate number of patients staying longer than 10 days were found in the group with congenital malformations. Seventy percent of the patients with multiple admissions (3.2% of all admissions) have genetic illness or congenital malformation.     

Effect of Chronic Desipramine Treatment on Dihydroalprenolol, Imipramine, and Desipramine Binding Sites: A Quantitative Autoradiographic Study in the Rat Brain

Desmethylimipramine (DMI) administered once daily for 10 days caused a significant decrease in beta-adrenergic receptor binding, as measured by quantitative autoradiography in discrete brain regions. The decrease was observed 72 h after the last injection throughout the cortex and in hippocampus but not in other regions, much richer in beta-receptors, such as the caudate, olfactory tubercle, superior colliculus, dorsomedial thalamus, substantia nigra, or pineal. The same paradigm did not affect imipramine (IMI) binding in the cortex or in regions with high concentrations of IMI binding sites. DMI binding was not decreased, either. Significant increases in DMI binding were observed in frontal cortex and in the ventral aspect of the bed nucleus of the stria terminalis. We conclude that a reduction in tricyclic binding is not a general phenomenon following chronic treatment with tricyclic antidepressants, and changes in binding, when they do occur, are not correlated with areas of high binding site density.     

The Impact of Prolonged Storage of Red Blood Cells on Cancer Survival

Background

The duration of storage of transfused red blood cells (RBC) has been associated with poor clinical outcomes in some studies. We sought to establish whether prolonged storage of transfused RBC in cancer patients influences overall survival (OS) or cancer recurrence.

Methods and Findings

Patients diagnosed with cancer at The Ottawa Regional Cancer Centre between January 01, 2000 and December 31, 2005 were included (n = 27,591) where 1,929 (7.0%) received RBC transfusions within one year from diagnosis. Transfused RBC units were categorized as “new” if stored for less than 14 days, “intermediate” if stored between 14 and 28 days and “old” if stored for more than 28 days. Baseline characteristics between the comparative groups were compared by ANOVA test. Categorical variables and continuous variables were compared using Chi-squared and Wilcoxan rank-sum tests respectively. Overall survival was not associated with duration of storage of transfused RBC with a median survival of 1.2, 1.7, 1.1 years for only new, intermediate and old RBC units respectively (p = 0.36). Cancer recurrence was significantly higher in patients who received a RBC transfusion than those who did not (56.3% vs 33.0% respectively; p<0.0001) but was not affected by the duration of storage of transfused RBC (p = 0.06). In multivariate analysis, lung cancer, advanced stage, chemotherapy, radiation, cancer-related surgery and cancer recurrence were associated with inferior OS (p<0.05), while age, advanced stage, lung cancer, and more than 6 units of blood transfused were associated with cancer recurrence (p<0.05). The duration of storage of RBC before transfusion was not associated with OS or cancer recurrence in multivariate analysis.

Conclusion

In patients diagnosed with cancer, the duration of storage of transfused RBC had no impact on OS or cancer recurrence. This suggests that our current RBC storage policy of providing RBC of variable duration of storage for patients with malignancy is safe.     

Bubble Stability Test Compared with Lecithin Assay in Prediction of Respiratory Distress Syndrome

A simple test for surfactant, utilizing bubble stability in ethanol, was performed in 106 samples of amniotic fluid obtained from 94 patients. Of these patients 80 delivered within 48 hours of the collection of the sample. The results were compared with the lecithin concentration in the same amniotic fluid samples and with the quality of respiration in the neonate. The test was “positive,” indicating fetal pulmonary maturity, in 37 cases and none of these infants developed respiratory distress syndrome (R.D.S.). In only one of these cases, however, was gestation less than 37 weeks. The test was “intermediate” or “negative” in 43 cases but in 35 of these infants respiration at birth was perfectly normal.Performed by the method described by its originators, this simple test gives too many false negative results to be of value in routine clinical practice, although a positive result is helpful. The concept of the test is ingenious, however, and further developments may be expected.     

A Study of the Work of a Medical Social Worker in a Group Medical Practice

An exploratory study was made to demonstrate the role, the work and the relationships of a full-time medical social worker in a group medical practice. Patients were seen on referral only, and a schedule for interview was developed for purposes of categorizing areas of social dysfunction. The following areas of dysfunction were studied: accommodation, job, social activities, family problems and medical diagnosis and/or treatment. A profile emerged of the patients referred as compared to patients in the practice as a whole. The “social sickness” in patients was more likely to exist between the ages of 20 and 44 years or over 65. It occurred more frequently in females and in individuals living alone or in a family of seven or more, in people from the lower social classes and the unemployed, retired people or actual or potential social isolates, those having a psychological illness, and those with degenerative disease of the circulatory or central nervous systems. It was less frequent in patients from a farm.     

NONOBSTRUCTIVE OLIGURIA—Differential Diagnosis

A review is presented of ten years'' experience with the differential diagnosis of oliguria, utilizing the standard tests of renal function with the addition of the phenolsulfonphthalein excretion and urinary chloride measurements. The histories of 60 patients seen in consultation because of 24-hour urinary volume of less than 400 ml were studied in order to clarify the value of these tests. Particular attention was given to the postoperative “dilution state,” the oliguria of which tends to mimic that of “acute tubular necrosis.”In only 25 per cent of the 60 cases was “acute tubular necrosis” responsible for the oliguria. In the remaining 75 per cent of patients, oliguria was due either to the effects of simple dehydration without tubular damage, or to tubular dysfunction on a physiologic rather than an organic basis. Thus, three out of four patients with oliguria required aggressive and specific fluid-electrolyte therapy, often with the intensive use of potassium. One out of four required the opposite in therapy—controlled dehydration without added potassium and, on occasion, peritoneal or extracorporeal dialysis, in order to allow six to ten days for tubular repair.     

Nitrate-regulated growth and cytokinin responses in seminal roots of barley

The influence of nitrate availability on growth of seminal roots, and root cytokinin levels, was studied in barley (Hordeum vulgare L. cv Golf). Nitrate was continuously supplied to initially N-starved seedlings at relative addition rates (RA) of 0.03 to 0.21 per day (standard cultures) or at RA 0.09 per day in split root cultures with the nitrate additions distributed in ratios of 100:0 or 80:20 to the two subroots. Data were collected both during a phase of acclimation (first 10 days of N additions) and in the acclimated stage (>10 days after onset of N additions). Limitation of whole-plant growth was observed at RA <0.15 per day. The lateral root frequency increased with RA in plants of equal chronological age. However, the lateral root frequency was related to root size rather than to RA; roots of uneven age but having comparable total root lengths also had comparable lateral root frequencies. Growth of individual subroots in split root systems during acclimation was proportional to the fraction of the total N addition that was fed to the root. All subroots had comparable relative growth rates in acclimated plants, and their lateral root frequency correlated with total root length in the same manner as in standard cultures. Onset of N additions in a 80:20 split root culture resulted in doublings of zeatin riboside (ZR) levels in shoots and in the “80” root, whereas the response of the “20” root was small. No effect of perturbed nitrate availability on xylem translocation of ZR was observed. The ZR levels remained higher in the “80” root during acclimation but returned to the level of the “20” root after acclimation. Root cytokinin levels and xylem translocation in acclimated standard cultures were unaffected by RA in the lower range but increased at high RA. Arguments for involvement of cytokinins in the nitrate-regulated growth response are discussed.     

Sex differences in the uptake and retention of imipramine and desmethylimipramine in the rat lung

¹⁴C-Imipramine was administered to male and female Sprague-Dawley rats and animals were sacrificed at 4, 8, 12, and 20 hours later. At all time points, total radioactivity in female lung was several-fold higher than in males. In addition, female lungs had a higher concentration of desmethylimipramine (DMI) as compared to imipramine than did male rat lungs. This was reflected by a higher conversion of imipramine to DMI by hepatic and pulmonary microsomes from female rats. Finally male rats cleared both imipramine and DMI from their lungs at a slower rate than did female rats.     

Quality along the Continuum: A Health Facility Assessment of Intrapartum and Postnatal Care in Ghana

Objective

To evaluate quality of routine and emergency intrapartum and postnatal care using a health facility assessment, and to estimate “effective coverage” of skilled attendance in Brong Ahafo, Ghana.

Methods

We conducted an assessment of all 86 health facilities in seven districts in Brong Ahafo. Using performance of key signal functions and the availability of relevant drugs, equipment and trained health professionals, we created composite quality categories in four dimensions: routine delivery care, emergency obstetric care (EmOC), emergency newborn care (EmNC) and non-medical quality. Linking the health facility assessment to surveillance data we estimated “effective coverage” of skilled attendance as the proportion of births in facilities of high quality.

Findings

Delivery care was offered in 64/86 facilities; only 3-13% fulfilled our requirements for the highest quality category in any dimension. Quality was lowest in the emergency care dimensions, with 63% and 58% of facilities categorized as “low” or “substandard” for EmOC and EmNC, respectively. This implies performing less than four EmOC or three EmNC signal functions, and/or employing less than two skilled health professionals, and/or that no health professionals were present during our visit. Routine delivery care was “low” or “substandard” in 39% of facilities, meaning 25/64 facilities performed less than six routine signal functions and/or had less than two skilled health professionals and/or less than one midwife. While 68% of births were in health facilities, only 18% were in facilities with “high” or “highest” quality in all dimensions.

Conclusion

Our comprehensive facility assessment showed that quality of routine and emergency intrapartum and postnatal care was generally low in the study region. While coverage with facility delivery was 68%, we estimated “effective coverage” of skilled attendance at 18%, thus revealing a large “quality gap.” Effective coverage could be a meaningful indicator of progress towards reducing maternal and newborn mortality.     

Is Early Tuberculosis Death Associated with Increased Tuberculosis Transmission?

Introduction

Tuberculosis (TB) is now a relatively uncommon disease in high income countries. As such, its diagnosis may be missed or delayed resulting in death before or shortly after the introduction of treatment. Whether early TB death is associated with increased TB transmission is unknown. To determine the transmission risk attributable to early TB death we undertook a case-control study.

Methods

All adults who were: (1) diagnosed with culture-positive pulmonary TB in the Province of Alberta, Canada between 1996 and 2012, and (2) died a TB-related death before or within the first 60 days of treatment, were identified. For each of these “cases” two sets of “controls” were randomly selected from among culture-positive pulmonary TB cases that survived beyond 60 days of treatment. “Controls” were matched by age, sex, population group, +/- smear status. Secondary cases of “cases” and “controls” were identified using conventional and molecular epidemiologic tools and compared. In addition, new infections were identified and compared in contacts of “cases” that died before treatment and contacts of their smear-matched “controls”. Conditional logistic regression was used to find associations in both univariate and multivariate analysis.

Results

“Cases” were as, but not more, likely than “controls” to transmit. This was so whether transmission was measured in terms of the number of “cases” and smear-unmatched or -matched “controls” that had a secondary case, the number of secondary cases that they had or the number of new infections found in contacts of “cases” that died before treatment and their smear-matched “controls”.

Conclusion

In a low TB incidence/low HIV prevalence country, pulmonary TB patients that die a TB-related death before or in the initial phase of treatment and pulmonary TB patients that survive beyond the initial phase of treatment are equally likely to transmit.     

Discriminating Survival Outcomes in Patients with Glioblastoma Using a Simulation-Based,Patient-Specific Response Metric

Accurate clinical assessment of a patient''s response to treatment for glioblastoma multiforme (GBM), the most malignant type of primary brain tumor, is undermined by the wide patient-to-patient variability in GBM dynamics and responsiveness to therapy. Using computational models that account for the unique geometry and kinetics of individual patients'' tumors, we developed a method for assessing treatment response that discriminates progression-free and overall survival following therapy for GBM. Applying these models as untreated virtual controls, we generate a patient-specific “Days Gained” response metric that estimates the number of days a therapy delayed imageable tumor progression. We assessed treatment response in terms of Days Gained scores for 33 patients at the time of their first MRI scan following first-line radiation therapy. Based on Kaplan-Meier analyses, patients with Days Gained scores of 100 or more had improved progression-free survival, and patients with scores of 117 or more had improved overall survival. Our results demonstrate that the Days Gained response metric calculated at the routinely acquired first post-radiation treatment time point provides prognostic information regarding progression and survival outcomes. Applied prospectively, our model-based approach has the potential to improve GBM treatment by accounting for patient-to-patient heterogeneity in GBM dynamics and responses to therapy.