- Email: [email protected]
Prevention of transient ischaemic attacks and strokes in the ederly
Bionzed
&
Pharmacother
(1995) 49, 382-384 0 Elsevier,
Paris
Notes
Thus A caused a very small increase in Na and urine output, and did not potentiate the effect of F. Although somewhat more effect of A has been seen in patients retaining less Na, complete resolution of edema has never been reported. Our results do not support the use of A either alone or in combination with F in NS patients and add strong evidence against the general validity of the “hypovolemic” concept. In addition we showed that F in the doses used was strongly natriuretic, despite reports that decreased protein binding may abolish its action.
Fluorescent PCR of minisatellite loci, either within or closely linked to tumour suppressor gene loci, was carried out. These included ~53, RB 1, APC, DCC, WTl and NM23. The samples studied were cases of transformed gastric MALToma where there was evidence of high grade lymphoma, low grade MALToma and a background of Helicobacter pylori associated gastritis. DNA from micro-dissected segments representative of each of these tissues was analysed by PCR. Allele imbalance and by implication loss of heterozygosity was found in 5 of 12 cases studied (2 at APC and 3 at DCC). There was no allele imbalance in the chronic gastritis material from these cases but in three cases, allele imbalance was found in the low grade MALToma. In the other two cases, the allele imbalance was found in the high grade tumour but not in the MALToma. The implications of this study are that in gastric MALToma, a condition associated with the histological features of a malignancy, that evidence of allele imbalance at tumour suppressor gene loci can be found. This genetic change is not present in the chronic gastritis material from these same patients which suggests that the change from chronic gastritis to gastric MALToma is associated with the development of genetic abnormalities. The fact that such tumours will regress with anti Helicobacter treatment in the form of antibiotic and antacids implies that although sufficient to cause a malignant phenotype in the presence of Helicobacter pylori, continued growth of the tumour is dependent upon the continued presence of the organism. We speculate that high grade transformation is the result of further changes which remove this dependence on the presence of the organism.
F Akcicek (1) Ege University School of Medicine, Izmir, Turkey
G Morgan (2) Leeds General Infirmary. Leeds LSI 3 EX, UK
Diuretic effects of intravenous albumin (A), furosemide (F) and their combination (A + F) in the nephrotic syndrome (NS). It has recently become apparent that sodium and volume retention in nephrotic syndrome (NS) cannot be accounted for by the classical “hypovolemia concept” in a large number of patients. Yet, based on this conception albumin infusion (A) has been claimed to increase Na excretion in NS patients and in particular to potentiate the action of diuretics. We therefore compared the effects of A (0.5 g/kg), F (60 mg IV followed by 40 mg/h during 4 hours) and A + F in 8 nephrotic patients with severe Na retention. Albumin infusion caused an increase of serum albumin from 1.73 to 2.36 g/l, with a mean rise in plasma volume of 30. Mean results were:
Na exe (uEq/min) Urine vol (ml/min)
(I)
Er Med
J
Control
A
F
17 0.75
0.54
934 8.49
1.24
AcF
884 9.21
1995;310: 162-3
H pylori and MALToma. There is good evidence both from human and animal models which links infection of the stomach with Helicobacter pylori and gastric MALToma. In a study looking at the genetic changes occurring during this process, a number of novel features were found.
(2) Lancer 1995;345:26-7
Prevention of transient ischaemic attacks and strokes in the ederly. No study has so far investigated the protective effect of antiplatelet drugs in patients older than 70 or 80 years. We analysed a subgroup of the 1,306 Finnish patients participating in the European Stroke Prevention
383
Notes
Study (ESPS) to evaluatae the effectiveness of drug treatment in different age groups. The ESPS investigated whether the combination of 330 mg aspirin and 75 mg dipyridamole three times a day was more effective than placebo in the secondary prevention of stroke or death in patients with previous ischaemic cerebral lesions. Of the 2,500 patients recruited, 1,306 were from a single centre in Kuopio, Finland. There was a clear increase in the risk of stroke or death with increasing age in the placebo group. In patients younger than 50, the frequency of the combined endpoints of ischemic stroke or death during two years of follow-up was 16%, increasing to 60% in patients older than 80 years. In the active treatment group, however, the frequency increased from 10% to only 20%. The reduction in the combined endpoint varied from 30% to 66.7% with the highest percentage reduction occurring in the oldest age group. The difference between the treatment groups was significant in all age groups of 50 and over. Patients with transient ischemic attacks and strokes should have secondary prevention with antithrombotic treatment regardless of age. University (3) Br Med
of Kuopio,
SF-70211
J Sivenius (3) Kuopio, Finland
/ 1995;310:25-6
ICI 182780: a new agent for breast cancer.
treatment
of
At present tamoxifen is the oestrogen antagonist of choice for the treatment of early and advanced breast cancer. The main problem in advanced breast cancer is that although approximately half of patients will respond to tamoxifen all ultimately become resistant. There is strong evidence in the literature that tamoxifen, in some way, can change from being a tumour antagonist to being an agonist and thus stimulate tumour growth as one cause of treatment failure. The specific anti-oestrogen ICI 182780 is structurally unlike tamoxifen which is a triphenylethylene. ICI 182780 is a steroidal anti-oestrogen. There is a long side chain attached to the 7 alpha position of the molecule which apparently sterically interfers with oestrogen receptor dimerisation and thus prevents binding of the receptor to the hormone response element. Thus it is likely that this agent will not have any agonist activity. In order to indirectly test this hypothesis we treated 19 patients who had responded and then progressed on tamoxifen or had failed tamoxifen as an adjuvant after surgery for breast cancer. Thirteen of the nineteen patients responded to montly intramuscular administration of ICI 182780. Durations of response were very long and the
median duration has not yet been reached at 18 months. No appreciable side effects were seen with this agent. Thus this study indicates that patients who fail on a triphenylethylene anti-oestrogen such as tamoxifen can respond to a steroidal antioestrogen when the tumour becomes resistant. This suggests that either tamoxifen failure is caused by stimulation of tumour growth by this agent or that, in some way, tamoxifen is sequested away from the oestrogen receptor thus allowing tumour growth to be restimulated by endogenous oestrogen. ICI 182780 is a promising agent to be used in tamoxifen failure but may also have advantages over tamoxifen in advanced breast cancer and in the adjuvant situation. Christie (4)
L.ancet
Hospital,
Manchester
A Howell M20 4BX,
(4) UK
1995;345:29-30
Serum cholesterol and risk of brain cancer. To investigate the role of serum cholesterol with subsequent risk of malignant brain cancer, the authors conducted a case-control study among roughly 160,000 members of the Kaiser Permanente of Northern California pre-paid health plan who had undergone multiphasic examination with serum cholesterol determination during the period 1964-72. Cancer diagnoses were identified by the Northern California Cancer Center, which manages a population-based registry that has participated in a national surveillance program since 1973, as well as by computerized hospital-discharge diagnoses. To confirm the latter diagnoses, the medical charts were obtained and reviewed. There were 85 women and 123 men diagnosed with brain cancer during the period beginning 5 years following the cholesterol determination and ending 31 December 1991. For each case, five controls, matched on age, year of examination, and sex, were selected. Conditional logistic regression was used to compute the odds ratio after adjustment for age, race, educational attainment, marital status, history of cigarette smoking, and alcohol intake. No consistent relationship of serum cholesterol level with risk of malignant brain cancer was observed (men, > 258 vs < 188 mg/dl, OR = 1.l with 95% confidence interval 0.52-2.2; women >258 vs < 180 mg/dl, OR = 0.58 with 95% confidence interval 0.24-1.4). The study differed from two earlier reports suggesting a positive association in that the determination of serum cholesterol was made well in advance of the diagnosis. Kaiser (5)
Br Med
Permanente,
J 1995;310:367-8
Oakland,
LJ Herrington CA 96411,
(5) USA
&
Pharmacother
(1995) 49, 382-384 0 Elsevier,
Paris
Notes
Thus A caused a very small increase in Na and urine output, and did not potentiate the effect of F. Although somewhat more effect of A has been seen in patients retaining less Na, complete resolution of edema has never been reported. Our results do not support the use of A either alone or in combination with F in NS patients and add strong evidence against the general validity of the “hypovolemic” concept. In addition we showed that F in the doses used was strongly natriuretic, despite reports that decreased protein binding may abolish its action.
Fluorescent PCR of minisatellite loci, either within or closely linked to tumour suppressor gene loci, was carried out. These included ~53, RB 1, APC, DCC, WTl and NM23. The samples studied were cases of transformed gastric MALToma where there was evidence of high grade lymphoma, low grade MALToma and a background of Helicobacter pylori associated gastritis. DNA from micro-dissected segments representative of each of these tissues was analysed by PCR. Allele imbalance and by implication loss of heterozygosity was found in 5 of 12 cases studied (2 at APC and 3 at DCC). There was no allele imbalance in the chronic gastritis material from these cases but in three cases, allele imbalance was found in the low grade MALToma. In the other two cases, the allele imbalance was found in the high grade tumour but not in the MALToma. The implications of this study are that in gastric MALToma, a condition associated with the histological features of a malignancy, that evidence of allele imbalance at tumour suppressor gene loci can be found. This genetic change is not present in the chronic gastritis material from these same patients which suggests that the change from chronic gastritis to gastric MALToma is associated with the development of genetic abnormalities. The fact that such tumours will regress with anti Helicobacter treatment in the form of antibiotic and antacids implies that although sufficient to cause a malignant phenotype in the presence of Helicobacter pylori, continued growth of the tumour is dependent upon the continued presence of the organism. We speculate that high grade transformation is the result of further changes which remove this dependence on the presence of the organism.
F Akcicek (1) Ege University School of Medicine, Izmir, Turkey
G Morgan (2) Leeds General Infirmary. Leeds LSI 3 EX, UK
Diuretic effects of intravenous albumin (A), furosemide (F) and their combination (A + F) in the nephrotic syndrome (NS). It has recently become apparent that sodium and volume retention in nephrotic syndrome (NS) cannot be accounted for by the classical “hypovolemia concept” in a large number of patients. Yet, based on this conception albumin infusion (A) has been claimed to increase Na excretion in NS patients and in particular to potentiate the action of diuretics. We therefore compared the effects of A (0.5 g/kg), F (60 mg IV followed by 40 mg/h during 4 hours) and A + F in 8 nephrotic patients with severe Na retention. Albumin infusion caused an increase of serum albumin from 1.73 to 2.36 g/l, with a mean rise in plasma volume of 30. Mean results were:
Na exe (uEq/min) Urine vol (ml/min)
(I)
Er Med
J
Control
A
F
17 0.75
0.54
934 8.49
1.24
AcF
884 9.21
1995;310: 162-3
H pylori and MALToma. There is good evidence both from human and animal models which links infection of the stomach with Helicobacter pylori and gastric MALToma. In a study looking at the genetic changes occurring during this process, a number of novel features were found.
(2) Lancer 1995;345:26-7
Prevention of transient ischaemic attacks and strokes in the ederly. No study has so far investigated the protective effect of antiplatelet drugs in patients older than 70 or 80 years. We analysed a subgroup of the 1,306 Finnish patients participating in the European Stroke Prevention
383
Notes
Study (ESPS) to evaluatae the effectiveness of drug treatment in different age groups. The ESPS investigated whether the combination of 330 mg aspirin and 75 mg dipyridamole three times a day was more effective than placebo in the secondary prevention of stroke or death in patients with previous ischaemic cerebral lesions. Of the 2,500 patients recruited, 1,306 were from a single centre in Kuopio, Finland. There was a clear increase in the risk of stroke or death with increasing age in the placebo group. In patients younger than 50, the frequency of the combined endpoints of ischemic stroke or death during two years of follow-up was 16%, increasing to 60% in patients older than 80 years. In the active treatment group, however, the frequency increased from 10% to only 20%. The reduction in the combined endpoint varied from 30% to 66.7% with the highest percentage reduction occurring in the oldest age group. The difference between the treatment groups was significant in all age groups of 50 and over. Patients with transient ischemic attacks and strokes should have secondary prevention with antithrombotic treatment regardless of age. University (3) Br Med
of Kuopio,
SF-70211
J Sivenius (3) Kuopio, Finland
/ 1995;310:25-6
ICI 182780: a new agent for breast cancer.
treatment
of
At present tamoxifen is the oestrogen antagonist of choice for the treatment of early and advanced breast cancer. The main problem in advanced breast cancer is that although approximately half of patients will respond to tamoxifen all ultimately become resistant. There is strong evidence in the literature that tamoxifen, in some way, can change from being a tumour antagonist to being an agonist and thus stimulate tumour growth as one cause of treatment failure. The specific anti-oestrogen ICI 182780 is structurally unlike tamoxifen which is a triphenylethylene. ICI 182780 is a steroidal anti-oestrogen. There is a long side chain attached to the 7 alpha position of the molecule which apparently sterically interfers with oestrogen receptor dimerisation and thus prevents binding of the receptor to the hormone response element. Thus it is likely that this agent will not have any agonist activity. In order to indirectly test this hypothesis we treated 19 patients who had responded and then progressed on tamoxifen or had failed tamoxifen as an adjuvant after surgery for breast cancer. Thirteen of the nineteen patients responded to montly intramuscular administration of ICI 182780. Durations of response were very long and the
median duration has not yet been reached at 18 months. No appreciable side effects were seen with this agent. Thus this study indicates that patients who fail on a triphenylethylene anti-oestrogen such as tamoxifen can respond to a steroidal antioestrogen when the tumour becomes resistant. This suggests that either tamoxifen failure is caused by stimulation of tumour growth by this agent or that, in some way, tamoxifen is sequested away from the oestrogen receptor thus allowing tumour growth to be restimulated by endogenous oestrogen. ICI 182780 is a promising agent to be used in tamoxifen failure but may also have advantages over tamoxifen in advanced breast cancer and in the adjuvant situation. Christie (4)
L.ancet
Hospital,
Manchester
A Howell M20 4BX,
(4) UK
1995;345:29-30
Serum cholesterol and risk of brain cancer. To investigate the role of serum cholesterol with subsequent risk of malignant brain cancer, the authors conducted a case-control study among roughly 160,000 members of the Kaiser Permanente of Northern California pre-paid health plan who had undergone multiphasic examination with serum cholesterol determination during the period 1964-72. Cancer diagnoses were identified by the Northern California Cancer Center, which manages a population-based registry that has participated in a national surveillance program since 1973, as well as by computerized hospital-discharge diagnoses. To confirm the latter diagnoses, the medical charts were obtained and reviewed. There were 85 women and 123 men diagnosed with brain cancer during the period beginning 5 years following the cholesterol determination and ending 31 December 1991. For each case, five controls, matched on age, year of examination, and sex, were selected. Conditional logistic regression was used to compute the odds ratio after adjustment for age, race, educational attainment, marital status, history of cigarette smoking, and alcohol intake. No consistent relationship of serum cholesterol level with risk of malignant brain cancer was observed (men, > 258 vs < 188 mg/dl, OR = 1.l with 95% confidence interval 0.52-2.2; women >258 vs < 180 mg/dl, OR = 0.58 with 95% confidence interval 0.24-1.4). The study differed from two earlier reports suggesting a positive association in that the determination of serum cholesterol was made well in advance of the diagnosis. Kaiser (5)
Br Med
Permanente,
J 1995;310:367-8
Oakland,
LJ Herrington CA 96411,
(5) USA