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.     

Proteins in luminal fluid of the ram excurrent ducts: changes in composition and evidence for differential endocytosis

Rete testis fluid (RTF) and luminal fluid collected by micropuncture at selected epididymal sites were analyzed to characterize the spectrum of proteins and to quantify the net gain or loss of total/bulk protein and androgen-binding protein (ABP) between successive regions within the ductus epididymidis. Based on one-dimensional SDS gel electrophoresis, the spectra of proteins in RTF and fluids from the proximal, central, and distal caput through proximal corpus epididymidis differed from each other. Concentrations of sperm, bulk protein, and ABP increased from the rete testis through the central caput epididymidis. Electron microscopic studies following intraluminal microinjections of RTF proteins conjugated to colloidal gold at specific sites in the excurrent ducts revealed that 145 times more protein-gold was endocytosed in the ductuli efferentes than in any of the four regions of the caput epididymidis. Thus, ductuli efferentes were the major extra-testicular site of endocytosis of bulk protein present in RTF; at least a portion of the uptake was specific. On a per sperm basis, the amount of protein present in the central caput epididymidis was less than 15% of that leaving the testis. Although most of the protein present in RTF (greater than or equal to 86 mg/d) must be absorbed in the ductuli efferentes and the initial segment of the epididymis and replaced by newly secreted proteins (greater than or equal to 34 mg/d), there was negligible loss of ABP in these regions. Net loss of ABP occurred primarily in the distal caput and proximal corpus epididymidis. These studies demonstrate that ABP is spared from endocytosis along with the bulk protein in RTF and conserved for functions in epididymal regions far distal to the site of bulk protein loss.     

The fate of N1'-methanesulphonyl-N4'-(9-acridinyl)-3'-methoxy-2',5'-cyclohexadiene- 1',4'-diimine (m-AQDI), the primary oxidative metabolite of amsacrine, in transformed Chinese hamster fibroblasts

The cytotoxicity of the anti-leukaemia drug amsacrine (m-AMSA) has been suggested to result from its oxidative metabolism to the corresponding quinonediimine, N1'-methanesulphonyl-N4'-(9-acridinyl)-3'-methoxy-2',5'-cyclohexad iene-1',4'- diimine (mAQDI). The metabolic fate of mAQDI was examined in cultured CHO cells (subline AA8) to identify the end products to be expected following oxidative metabolism of m-AMSA. [Acridinyl-G-3H]-m-AQDI was rapidly accumulated by AA8 cells in phosphate buffered saline with complete conversion in less than one minute to m-AMSA, macromolecular adducts and polar low molecular weight species, each of these three classes being formed in approximately equal amounts. Two of the polar products were chromatographically identical to those formed on reaction of m-AQDI with reduced glutathione. These were identified by 1H NMR spectroscopy as the 1,4-addition product 5'-(S-glutathionyl)-m-AMSA and the previously unreported isomeric 6'-(S-glutathionyl)-m-AMSA. These thiol adducts were also formed rapidly from m-AQDI in deproteinized cell lysates indicating a non-enzymatic process, although the possibility of enzymatic catalysis in intact cells has not been eliminated. The absence of such products in AA8 cells after treatment with m-AMSA places an upper limit of 1% per hour on the rate of its oxidative metabolism in these cells and suggests that generation of m-AQDI is unlikely to be responsible for the cytotoxicity of m-AMSA in cultured tumour cells.     

Effect of the beta-adrenoceptor agonist clenbuterol and phytohaemagglutinin on growth, protein synthesis and polyamine metabolism of tissues of the rat.

1. The kidney bean lectin, phytohaemagglutinin (PHA), induced a marked atrophy of skeletal muscle which was evident from the changes in tissue composition (protein, RNA, DNA and polyamine content) and from the reduction in weight and protein synthesis of hind leg muscles of rats fed on kidney bean-diets for four days. The beta-adrenoceptor agonist, clenbuterol, induced skeletal muscle hypertrophy by transiently stimulating protein synthesis. As a consequence, the muscle loss caused by a short exposure to PHA was, in part, ameliorated by clenbuterol treatment. 2. Cardiac muscle was affected to a lesser extent than skeletal muscle by both clenbuterol and the lectin. However, there was evidence that protein synthesis in heart was reduced by PHA. 3. PHA had opposite effects on the gut, the lectin-induced hyperplasia of the jejunum was accompanied by a large increase in protein synthesis. Clenbuterol alone had no effect on the jejunum whereas a combination of PHA and clenbuterol appeared to exacerbate the effect of the lectin on gut. 4. Both the lectin-induced gut growth and the hypertrophy of skeletal muscle caused by clenbuterol were preceded by the accumulation of polyamines in the respective tissues. Of particular note was the observation that a significant increase in the proportion of the intraperitoneally injected 14C-labelled spermidine or putrescine taken up by the growing tissues could be detected by the second day. Therefore, the measurement of uptake of labelled polyamines may be used as a sensitive indicator of early alterations in tissue metabolism.     

An observer blind trial of co-amoxiclav versus cefuroxime plus metronidazole in the prevention of postoperative wound infection after general surgery

A consecutive series of 509 patients undergoing abdominal surgery were entered into a randomized, observer and patient blind, controlled, prospective, study to evaluate the efficiency of co-amoxiclav (‘Augmentin’, SmithKline Beecham, UK) compared with cefuroxime (‘Zinacef’ Glaxo, UK) plus metronidazole (Flagyl, M&B, UK) for the prevention of postoperative wound infections. One or three doses of antibiotics were given depending on the type of surgery and operative factors. Co-amoxiclav was given to 230 patients with a total wound infection rate of 5·6% and cefuroxime plus metronidazole were given to 225 patients with a total wound infection rate of 3%. The difference between infection rates was not significant. Both groups were comparable in terms of demographic details, type and duration of surgery, risk factors associated with surgical procedures and postoperative management. Although not statistically significant, a difference in the wound infection rate for those patients undergoing colorectal surgery was seen: for the co-amoxiclav group and for the cefuroxime/ metronidazole group. The estimated cost to our hospital (October 1993) of one dose of co-amoxiclav was less that half the cost of cefuroxime and metronidazole. This study demonstrates that co-amoxiclav is an effective prophylactic antibiotic for abdominal surgery.