The effect of low dose lofepramine in depressed elderly patients in general medical wards.

A double-blind randomised controlled trial of the effect of low dose lofepramine (70 mg once daily) against placebo was carried out on depressed elderly inpatients on general medical wards for the elderly, comparing measures of depression and side-effects between the randomised groups. Patients were identified for the study using the Geriatric Depression Scale (GDS) and the Brief Assessment Schedule Depression Cards (BASDEC). Sixty-three subjects were randomised: 46 patients completed the entire trial of 28 days treatment. BASDEC and GDS were administered on day 8 post-admission, and depressed patients were randomised double-blind to either low dose lofepramine (70 mg daily) (n = 23) or placebo (n = 23). Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale (MADRS) on days 8, 18 and 36 post-admission. Both groups improved by a similar amount during the trial. Lofepramine tended to be more effective than placebo in those patients who were more depressed (GDS > or = 18). On the other hand, subjects who were less depressed (i.e. GDS < 18) improved more on placebo than lofepramine. Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks. However, low dose lofepramine is not indicated for mild (GDS 15-18) depression.     

Does multi-vessel off-pump coronary artery bypass grafting reduce post operative morbidity compared to on-pump CABG?

Background Cardiopulmonary bypass (CPB) may contribute to the complications and it is assumed that eliminating cardiopulmonary bypass has the potential of reducing post operative morbidity after coronary artery bypass grafting (CABG). The study was carried out to compare mortality and morbidity in the off-pump and on-pump CABG groups. Methods We prospectively analysed 200 patients undergoing CABG. Group A consists of 100 patients underwent multi-vessel off-pump CABG and group B consists of 100 patients underwent CABG with CPB. The incidence of complications (mortality, re-exploration for bleeding, myocardial infarction, atrial fibrillation, neurological events, new onset renal failure (s. creatinine>1.6 mg/dL) pulmonary complications, length of ICU stay and hospital stay were recorded, analysed and compared. Results OPCAB patients received 2.73±0.61 grafts/patient and on-pump CABG patients received 3.39±0.75 grafts/patient (p value<0.00001). There was no significant statistical difference in mortality, incidence of stroke between OPCAB and CABG with CPB patients. Length of ICU stay was 32.84±4.22 vs 44.85±7.18 hrs (p value<0.00001) and hospital stay was 6.52±0.69 vs 7.94±0.92 days (p value<0.00001) between group A and group B respectively. Incidence of atrial fibrillation was less in OPCAB group 7% vs 12% although it was statistically not significant (p value 0.33). It was observed in our study that there was no significant deference in worsening of existing renal failure between on-pump CABG and OPCAB 6% vs 2% (P value 0.28). Blood utilization was significantly less in OPCAB group (p value<0.001). Conclusion There was no statistically significant difference in terms of mortality, incidence of stroke and new onset renal failure in both groups. But there was lesser incidence of post operative atrial fibrillation, worsening of existing renal failure in off-pump group though statistically not significant. There was significant reduction in blood utilization, length of ICU and hospital stay in OPCAB group.     

Effects of risk-associated human dietary macrocomponents on processes related to carcinogenesis in human-flora-associated (HFA) rats

Dietary fat, beef protein and fibre have been shown to modulatecancer risk in humans and the present study examined the biologicaleffects in human-flora-associated (HFA) rats of altering intakelevels within the normal human range. Two control groups, oneHFA and the other germfree (GF), consumed a human diet low infat, fibre and beef for 4 weeks; three other groups consumedhuman diets similar except for independent 3-fold increasesin fat, beef protein or fibre. After 2 weeks on the diets, magneticallyrecoverable microcapsules were given orally to the rats andsubsequently recovered from the faeces to assess endogenouscross-linking agents. After 4 weeks, measurements were madeof gut microfloral enzyme activities, hepatic activation ofdietary mutagens and hepatic DNA adducts by ³²P-postlabelling.Activation in vitro of the dietary mutagens 2-amino-3-methyl-3H-imidazo[4,5-f]quinolline (IQ) and 2-amino-l-methyl-6- phenytimidazo[4,5-b]pyridine(PhIP) by hepatic S9, formation of endogenous hepatic DNA adductsin vivo and the ß-glucuronidase activity of caecalcontents were all increased in the sequence high fat > highfibre > high beef = control. Of the two DNA adducts foundin all HFA rats, only one was present in GF controls, indicatingthat the human gut microflora (subject to human dietary modulation)either releases a DNA-adducting product able to act outsidethe gastrointestinal tract, or stimulates the generation ofsuch a product by mammalian processes. Caecal nitrate reductaseactivity was highest in rats fed the high beef diet, whilstentrapment of cross-linking agents was highest in those fedthe high fibre diet. These results show that risk-related componentsof human diets interact with human gut microflora to modulatethe production of endogenous DNA-adducting and cross-linkingsubstances.     

The index manic episode in juvenile-onset bipolar disorder: the pattern of recovery.

OBJECTIVE: Recent studies of patients with juvenile bipolar disorder report low rates of recovery and high rates of chronicity. However, we lack data on the short-term outcome. This study examines the pattern of recovery from the index episode in an aggressively treated juvenile sample. METHOD: We assessed 25 subjects (< 16 years) with a diagnosis of mania, using the Diagnostic Interview for Children and Adolescents-Revised) (DICA-R), Young Mania Rating Scale (YMRS), and Children's Global Assessment Scale (CGAS) at intake and at 3 and 6 months. We studied the time taken to recover from the index episode, the level of functioning, and the factors predicting them. RESULTS: After 6 months, 24 (96%) subjects had recovered from the index manic episode. The median time to recovery was 27 days. Total episode length was significantly longer among those with previous affective episodes. CONCLUSIONS: The findings suggest that juvenile-onset mania has high rates of recovery and low rates of chronicity. These differences from the existing literature need further exploration.     

Timed treatment of the arthritic diseases: a review and hypothesis.

Evidence has been accumulating regarding the importance of biological rhythms in the diagnosis and treatment of a variety of diseases and disorders. Increasingly, the arthritides have shown statistically quantifiable rhythmic parameters. Included in the latter group are joint pain and joint size. In addition, a number of drugs used to treat rheumatic diseases have varying therapeutic and toxic effects based on the time of day of administration. Among these drug classes are nonsteroidal antiinflammatory drugs, glucocorticoids, and a number of cytostatic agents. In the last group of agents, experience in treating malignant disease suggests that time-specified treatment may reduce the toxic effects of low-dose cytostatic treatment of rheumatoid arthritis (RA) and related diseases. This article reviews that evidence and suggests a rationale for the timed treatment of RA with methotrexate.     

Unilateral proptosis secondary to diffuse condensing osteomyelitis

Osteomyelitis of the skull is an uncommon disease in the present days, mainly due to the advent of modern and more effective antibiotics. Hematogenous osteomyelitis is very rare. Osteomyelitis of the skull is usually not associated with sclerosis which is commonly seen in the rest of the skeleton. There are only few occasional case reports of condensing osteomyelitis wherein there was sclerosis of the bone associated with osteomyelitis of the skull and epidural abscess. An unusual case of diffuse condensing osteomyelitis of the skull producing unilateral proptosis is reported. The clinical, radiological features and microbiological aspects are presented. The proptosis was treated by excision of the bone behind the eyeball and thus relieving the proptosis and the impaired vision. The patient was given broad spectrum antibiotics for a period of two months. Further management problems are discussed.     

Lithium and memory: a review

This paper reviews systematic clinical studies suggesting memory and cognitive impairment in patients suffering from unipolar and bipolar affective disorders treated with lithium. A number of studies failed, however, to demonstrate lithium induced memory deficits. Thus, the results of studies were equivocal. This lack of empirical consensus was in part due to the heterogeneity of samples and a variety of methodological and design problems. The definition of short- and long-term memory was often arbitrary and lacked standard criteria. Some studies revealed a stability of the memory test scores over time and showed that subjective complaints of memory impairment were correlated with depression. The authors also reviewed studies examining the effects of lithium on cognition and memory of healthy control subjects. In animal research it was difficult at times to distinguish between toxic and pharmacologic effects of lithium. There is a need for prospective studies of the effect of lithium in large samples of patients using refined memory tests.     

Influence of a calcium dependent protease inhibitor on platelet activation and secretion

Continuous proteolysis resulting in consumption of major cytoskeletal proteins may be essential for platelet activation and aggregation. In this study we evaluated the effect of a known protease inhibitor, Leupeptin, on agonist induced platelet aggregation and secretion. Platelets exposed to 10 ugs/ml of Leupeptin did not aggregate in response to the action of thrombin (0.2u/ml). However, a concentration of Leupeptin as high as 250 ugs/ml did not prevent arachidonate induced aggregation and secretion. Leupeptin (100 ugs/ml) effectively blocked thrombin (0.2 u/ml) induced elevation of cytosolic calcium, but did not affect arachidonate induced elevation of platelet intracellular calcium levels. At a concentration of 100 ug/ml, Leupeptin effectively blocked thrombin (0.5u/ml) induced clot formation of platelet poor plasma, suggesting that it can exert its effect on thrombin by preventing fibrinogen degradation. Effective K_i for the competitive inhibition of thrombin induced hydrolysis of a chromogenic substrate, S2238, by Leupeptin was 2.4 uM. Leupeptin inhibition of platelet function was reversible by washing platelets free of the polypeptide. Results of our study demonstrate that Leupeptin inhibits thrombin induced platelet activation, probably by interfering with its proteolytic activity on the platelet surface membrane. However, inhibition of platelet surface membrane associated proteases did not prevent activation of platelets by other agonists.