New experimental data on the relationship between diabetes mellitus and magnesium. Diabetes mellitus is the most frequent chronic disease associated with secondary magnesium deficit. Hypomagnesaemia is a central feature of the deficit, which is often reported in experimental and clinical forms of the disease. In diabetic rats as in man, plasma magnesium concentrations may correlate inversely with the degree of hyperglycaemia. The duration of the disease also appears to be relevant. The hypomagnesaemia of diabetes might be expected to affect intracellular concentrations of the ion. However, although some animal and clinical studies have reported subnormal magnesium concentrations in blood cells, bone, and soft tissues of diabetics, the relationship between plasma magnesium concentration and intracellular level of the ion is inconsistent. Clinical studies have speculated on a potential link between the magnesium deficit of diabetes and several diabetic complications, including cardiovascular problems and retinopathy. Recent experimental studies are largely supportive of such a link; myocardial disorders associated with magnesium deficiency have been reported in diabetic mice and rabbits. It is possible that a common mechanism involving magnesium may be responsible for some of the diverse complications of diabetes. The aetiology of hypomagnesaemia in diabetes is complex. Nevertheless, plasma magnesium concentrations are ultimately determined by four processes: intake, gastrointestinal absorption, redistribution within body pools, and urinary excretion. This review considers in turn the potential role of each of these processes in the development of diabetic hypomagnesaemia. Both experimental and clinical studies suggest that hypermagnesiuria may be the major factor involved. Recent animal studies have described a specific renal tubular magnesium defect in diabetes, which, together with the osmotic diuresis, is responsible for large magnesium losses. The precise cause of the defect is unknown, but it may relate to the prolonged hyperglycaemia, insulinopenia, disturbance of phosphate metabolism, or other hormonal changes which characterize the disease.


Relationship between neurological diseases due to aluminium load, especially amyotrophic lateral sclerosis, and magnesium status. The correlation between kinetic metal behaviour and the degenerative process in the central nervous system (CNS) tissues of magnesium (Mg) deprived animals was examined, with particular reference to the levels and ratios of Mg, calcium (Ca), and aluminium (Al). Al content in the CNS tissue was high in the groups fed low Mg and low Mg + low Ca diets, as well as those supplemented with Al. In the group given a normal Mg, normal Ca with high Al diet, Al content in the CNS tissue showed no difference compared with that of the control group, although the concentration of Al in the serum was high. It was observed that Al content tended to rise with an increase in the Mg/Ca ratio in the CNS tissue. There was neither atrophy nor degeneration of the anterior horn cells of the spinal cord, nor demyelination of the pyramidal tract, which are characteristic of the pathology of amyotrophic lateral sclerosis. The cell body, nucleus, and nucleolus of the spinal neurones, however, appeared to diminish in size in the groups fed a low Mg diet and low Mg, low Ca with surplus Al diet. On the basis of these findings, it is speculated that Mg depletion, by increasing the Ca/Mg ratio in the CNS tissues, accelerates the uptake of Al into the brain, and this may later be involved in the development of the degenerative process.


A review of biointeractions of Ni and Mg. I. Enzyme, endocrine, transport, and skeletal systems. Magnesium (Mg) and nickel (Ni) are biologically active elements in higher animals. Recent studies in vivo as well as in vitro point to interactions of Ni and Mg; non-immunological roles of these elements are reviewed here. Ni and Mg play roles in some of the same enzyme and endocrine systems, body and cell structures, and transport systems. Mg status has determined some responses to dietary Ni. Information available at this time is inadequate to permit assessment of all functions of Mg and Ni and their interactions in human populations. Evidence to date, however, warrants further investigation of the nutritional and metabolic relationships between these elements, over wide ranges of dietary intakes or exposure levels.


A review of biointeractions of Ni and Mg. II. Immune system and oncology. Reports of interactions, in vivo and in vitro, between Ni and Mg in humoral and cellular immunity, hypersensitivity and inflammation, and in tumourigenesis are explored from a mechanistic viewpoint. Although Mg is present in much larger concentrations in normal mammalian systems than Ni, similar chemical and physical properties may allow Ni to exchange for Mg at reactive sites with damaging consequences to living organisms. Consequences of such exchanges could involve reduced immunocompetence and related carcinogenic transformation of cells. Mg status and environmental exposure to Ni are conceivable antecedents to possible biological sequelae in humans.


The management of denial in cancer patients. Faced with a diagnosis of cancer, many patients react initially with a kind of numbed disbelief that is a form of denial. In the majority of cases, this reaction is subsequently replaced by other coping responses. Some patients, however, continue to use denial. Clinically, it is useful to categorize denial as follows: (1) complete denial, (2) denial of implications of a diagnosis of cancer, (3) denial of affect. Denial, particularly if complete, can have adverse effects in terms of delay in seeking treatment and noncompliance with treatment. But there are also certain advantages. Denial is associated with reduction in psychological distress, and there is preliminary evidence suggesting that it may be associated with prolonged duration of survival in women with nonmetastatic breast cancer. Although there are no hard and fast guidelines for the psychological management of patients who use denial, four possible management scenarios are provided.


High-dose chemotherapy with autologous stem cell support for breast cancer. Breast cancer is a major public health issue, expected to affect one out of nine women over a lifetime. High-dose chemotherapy with autologous stem cell support is a current approach to the management of metastatic breast cancer and high-risk primary breast cancer. This review considers the effectiveness of this modality in the treatment of breast cancer in an effort to define its role in overall patient management. Current research directions, including technical advances aimed at reducing toxicity, are discussed. Finally, controversies regarding the role of third-party payers in the investigational process are considered.


Analgesia in children with sickle cell crisis: comparison of intermittent opioids vs. continuous intravenous infusion of morphine and placebo-controlled study of oxygen inhalation. The objectives of the study were to compare the efficacy and safety of a continuous infusion (CIV) of morphine and intermittent parenteral opioids (IPO) in children with sickle cell vaso-occlusive crises (VOCs); to determine whether 50% oxygen administration through a face mask can reduce the duration of severe pain in patients receiving CIV morphine; and to measure morphine concentration at steady state for pharmacokinetic and pharmacodynamic analysis in patients receiving CIV morphine. The study was designed as a prospective, controlled, "before-and-after" evaluation of two different analgesic regimens. For patients receiving CIV morphine, there was a randomized, double-blind, placebo-controlled study of O2 vs. air. The patients were 66 children with sickle cell disease, 3-18 years old, requiring opioid therapy for severe VOC (32 patients in phase A, 34 in phase B). The analgesic regimens were as follows: phase A: meperidine, morphine, or codeine IM or IV bolus every 3 or 4 hours; phase B: morphine sulfate, loading dose 0.15 mg followed by CIV 0.04 mg/kg/hr. The infusion rate was adjusted every 8 hours according to pain and/or symptoms of opioid toxicity. Pain assessment was by behavioral observation (BPS). In terms of results, the mean opioid dose (morphine equivalent) was similar in both groups (0.032 +/- 0.020 mg/kg/hr in phase A and 0.035 +/- 0.011 in phase B). However, the duration of severe pain was significantly shorter in phase B (0.9 +/- 1.0 days) than in phase A (2.0 +/- 1.8 days). No severe opioid toxicity was observed in either group. Oxygen did not shorten the duration of severe pain compared to the placebo group (0.94 +/- 1.08 and 0.95 +/- 1.19 days, respectively) nor did it prevent the appearance of new pain sites. Pharmacokinetic analysis was performed in 24 patients of phase B. Total body clearance (TBC) of morphine was greater in children before puberty than after (40.4 +/- 10 vs. 28 +/- 11 mL/kg/min; p < 0.05). In conclusion, in children with severe VOCs, continuous infusion of morphine provides better analgesia than intermittent opioid therapy. Fifty percent oxygen inhalation had no effect on the duration of pain.


Intravenous immunoglobulin prophylaxis in children with acute leukemia following exposure to varicella. The high risk of varicella in immunocompromised children has been well documented. With the aim of diminishing this risk, attempts have been made to modify or prevent varicella by passive immunization. From September 1985 to March 1991, five children with leukemia, having a total of seven episodes of intimate exposure to varicella, received a single dose (200 mg/kg) of intravenous immunoglobulin (IVIG) within 3 days of exposure. The patients included four children with acute lymphoblastic leukemia and one child with myelodysplastic syndrome in acute myeloblastic leukemic transformation. None of the five children developed varicella following IVIG infusion. No side effects were observed. IVIG appears to be an effective and safe alternative for preventing varicella in immunocompromised patients upon intimate exposure, when zoster immunoglobulin or varicella-zoster immunoglobulin is unavailable, as in Taiwan.


History of pediatric hematology and oncology in Finland: a brief review. The history of Finnish pediatric hematology started in the late 1940s, but this field of pediatrics was not officially acknowledged before 1979. The Children's Hospital, University of Helsinki started hematological services in 1950 but at that time there was no position for a specialist--it was a "spare time" work until 1980 when a hematology/oncology ward was established led by a full time specialist. Since the late 1950s the pediatric department of the Aurora Hospital in Helsinki has made an important contribution to the development of Finnish pediatric hematology. The Blood Transfusion Service of the Finnish Red Cross has also played an important role in Finnish pediatric hematology. The remaining four University Hospitals have now established wards for pediatric Hematology/oncology.


Reevaluation of iron absorption and serum ferritin in beta-thalassemia intermedia. In order to reassess the need for iron chelation therapy in nontransfused patients with beta-thalassemia intermedia, serum ferritin level and ferrous iron absorption from the gastrointestinal system were measured in 43 (23 male and 20 female) patients (mean age 13.4 +/- 7.5). The mean hemoglobin value was 8.6 +/- 1.3 g/dL and serum ferritin 303 +/- 207 ng/mL. Absorption of ferrous iron salt was determined in 21 patients by measuring serum iron before and 3 hours after giving ferrous salt orally at 1 mg/kg. The means of the increase in serum iron values were 39 +/- 45, 105 +/- 46, and 224 +/- 112 micrograms/dL in patients with beta-thalassemia intermedia, normal subjects, and patients with iron deficiency anemia respectively. Differences in the means in three groups were significant (p < 0.001). This study shows that iron absorption from the gastrointestinal system as ferrous salt is not accelerated in patients with beta-thalassemia intermedia. The serum ferritin level in these patients is not high enough to necessitate iron chelation therapy.


Second bone marrow transplantation in eight children. Between 1985 and 1989, eight children underwent two successive bone marrow transplantations. The initial disease was chronic myelomonocytic leukemia in three patients, chronic myelocytic leukemia in two, acute M7 nonlymphoblastic leukemia in one, sickle cell anemia in one, and thalassemia major in one. The preparation in view of the second grafting included high-dose chemotherapy in all patients, associated with antithymocytic globulin transfusion and total nodal irradiation in three patients. Hematological recovery was similar after both graftings. Infectious complications were not more common following the second graft than after the first one. On the other hand, the rates of rejection and graft-versus-host disease were lower, probably due to a more intensive immunosuppressive therapy. The prognosis of chronic leukemia relapsing after a first graft does not seem to be improved by a second attempt.


Renal revascularization in high-risk patients: the role of iliac renal bypass. Between 1984 and 1989, 29 iliac renal artery bypasses were performed in 29 patients (mean age 67.8 years) with severe renovascular disease due to atheroma. The indication for renal artery reconstruction was hypertension in all patients, which was associated with kidney failure in 16 cases. In six cases, reconstruction was performed after failure or complications of percutaneous transluminal angioplasty. The bypass was constructed with polytetrafluoroethylene in 24 cases (83%) and vein graft in five cases (17%). There was no postoperative mortality. All bypasses were found to be patent on duplex scanning or digital subtraction arteriograms. One patient was lost to follow-up. Mean follow-up was 23.2 months. One patient died of acute kidney failure, probably related to occlusion of the bypass. Hypertension improved in 22 cases (79%), was cured in two cases (7%), and remained unchanged in four (14%). Renal function remained unchanged in six cases (40%) and improved in nine (60%). Iliac-to-renal artery bypass seems to be the surgical renal revascularization modality best adapted to high-risk patients or those who have severe atheroma. Additionally, this technique enables rapid treatment of failures or complications of percutaneous transluminal angioplasty of the renal artery.


The evolution of carotid and coronary artery disease after operation for carotid stenosis. We followed 278 consecutive patients undergoing carotid artery surgery between January 1985 and December 1989 using a computerized surveillance program file with automatic carotid and coronary artery follow-up investigations every six months. Combined postoperative neurologic mortality and morbidity was 1.7%. During the mean follow-up period of 30 months, 10 patients died, four due to myocardial infarction. Actuarial rates of survival and freedom from cerebral vascular accidents at 36 months were 94% and 95.8%, respectively. No fatalities due to cerebral vascular accidents occurred during follow-up. Eleven patients had myocardial infarction, an actuarial rate of 6% at 36 months; 18 patients experienced angina pectoris, while seven sustained silent electrical myocardial ischemia. Findings on myocardial angioscintiscans and coronary artery arteriograms led to four aortocoronary bypasses and seven percutaneous coronary artery dilatations. Duplex scanning documented three asymptomatic carotid restenoses of > or = 80%, which were operated upon, and 32 contralateral carotid artery stenoses ranging between 80% and 99%, 24 of which were asymptomatic. Twenty-eight patients underwent secondary contralateral carotid artery revascularization. No one with contralateral carotid artery stenosis < 80% experienced a carotid artery ischemic event. These results clearly show the value of cardiac and neurologic surveillance of patients operated on for carotid artery stenosis.


Aortic false aneurysms after prosthetic reconstruction of the infrarenal aorta. False aneurysm of the infrarenal aorta was found at the site of proximal anastomosis in 13 patients after vascular reconstruction for lower limb arterial disease. The grafts involved were aortoprosthetic in one patient, aortobiiliac in two patients, and aortobifemoral in 10 patients. They had been implanted eight years prior to reoperation on the average (range six months to 15 years). False aneurysm was diagnosed because of abdominal pain in four cases, embolism in two cases, intestinal hemorrhage in one case, and during routine sonographic or computed tomographic (CT) scan surveillance in the six other cases. Femoral false aneurysm was associated in eight of 10 cases with femoral anastomoses. Aortic false aneurysms were repaired by interposition of a prosthetic tube between the infrarenal aorta and the original prosthetic graft in 11 cases and by changing the aortobifemoral graft in two cases. In one further case, repair was accomplished by implanting an aortobifemoral prosthetic graft laterally on a prosthetic tube interposed between the infrarenal aorta and the body of the original prosthetic graft, which continued to irrigate the internal iliac arteries. There was no mortality. Thrombosis of a prosthetic branch occurred in one case and was treated by thrombectomy. One patient underwent reoperation for intestinal obstruction. Two others had distal embolism responsible for toe necrosis. Anastomotic false aneurysms should be looked for routinely during the surveillance of prosthetic grafts implanted on the infrarenal aorta, especially when femoral false aneurysm is found. Preservation of pelvic vascularization must be an integral part of management.


Changing pattern of treatment policies invalidates the use of C-reactive protein level and hyponatremia as indicators of sepsis in children with malignancies. We evaluated serum C-reactive protein (CRP) level and serum sodium concentration as early indicators of bacteremia in neutropenic children in two different series in 1983-1984 (49 bacteremias) and 1989-1990 (29 bacteremias). During the earlier period, the goal was to avoid unnecessary antimicrobial therapy. Currently a neutropenic patient is placed on antimicrobial therapy at the first sign of fever. In 1983-1984 the serum CRP concentration was elevated in every case, whereas in 1989-1990 it was normal in 34% cases (P = .0001). Hyponatremia was detected on admission in 84% and 52% cases (P = .0001). The urinary sodium concentration was elevated in most cases. The mortality in bacteremia was 22% in 1983-1984 compared to 3% (P = .025) in 1989-1990. Prompt initiation of empirical antimicrobial therapy in children with fever and neutropenia invalidates the use of hyponatremia and an elevated CRP level as early indicators of sepsis.


Late results of palmar arch bypass in the treatment of digital trophic disorders. This study reports the late results of eight palmar bypass procedures performed between 1983 and 1988 in eight men patients with a mean age of 43 years old, who presented with unilateral digital trophic disorders. The origin of the arterial lesions was post-traumatic in four cases, embolic in three cases, and aneurysmal in one. The procedures performed included four radiopalmar bypasses, two ulnar-palmar bypasses, one distal radial bypass and one palmopalmar bypass. In all cases, the replacement conduit used was the superficial radial vein retrieved from the wrist. There were no complications observed in this short series. All fingers healed within three weeks' time after excision of necrotic lesions. During a mean follow-up of 66 months, two bypasses became thrombosed, leading to amputation of the distal phalanx of a thumb in one patient while the remaining six bypasses remained patent, three of them for more than seven years. In the presence of trophic changes of the fingers, palmar arch bypasses, whenever feasible, are more effective at long-term and less aggressive than the usually proposed thoracic sympathectomy.


Saphenous vein endothelium-dependent relaxation in patients with peripheral vascular disease. In vitro vasomotor responses of saphenous veins of 15 patients undergoing peripheral vascular bypass procedures were studied. Vessels were harvested by standard techniques, sectioned into 4 mm rings, and suspended in organ baths under isometric tension. Stimulation with cumulative doses of norepinephrine revealed a -logED50 of 6.85 +/- 0.12 M and maximal tension of 8.64 +/- 1.77 g. Patient characteristics suggesting high maximal response (by univariate analysis) included male sex (male 11.69 +/- 2.49 g versus female 5.08 +/- 1.69 g; p = 0.058). Intact and denuded rings were additionally tested for endothelium-dependent relaxation following submaximal norepinephrine precontraction. The vessels relaxed in response to acetylcholine (maximal relaxation 31.1 +/- 10.7% at 1 x 10(-6) M), calcium ionophore A23187 (85.3 +/- 11.8% at 1 x 10(-5) M), and sodium nitroprusside (150.8 +/- 15.2% at 1 x 10(-5) M), but only acetylcholine relaxation was completely endothelium-dependent. Calcium ionophore A23187 relaxation was partially dependent on the endothelium while sodium nitroprusside relaxation was entirely endothelium-independent. Negligible relaxation was observed in response to adenosine diphosphate (ADP) (12.1 +/- 12.8% at 1 x 10(-5) M) while histamine and serotonin caused additional contraction only. We concluded that, in patients undergoing vascular surgical procedures, the saphenous vein (1) demonstrates variable contractile function which appears to be greater in males following spinal anesthesia, and (2) exhibits moderate endothelium-dependent relaxation in response to acetylcholine and calcium ionophore A23187 but not to ADP, histamine, or serotonin.


Increased intestinal permeability: implications for thoracoabdominal aneurysm repair. Coagulopathy and massive bleeding plays a major role in the mortality of thoraco-abdominal aneurysm repair. Increasing supraceliac aortic cross-clamp time from 0 to 90 minutes increases the degree of disseminated intravascular coagulation, which occurs as a result of occlusion and reperfusion of the superior mesenteric artery. The purpose of this study was to investigate the mechanism of the superior mesenteric artery reperfusion disseminated intravascular coagulation. Twenty dogs were divided into four groups: cross-clamp time of 30 minutes; cross-clamp time of 60 minutes; cross-clamp time of 90 minutes; and control. Permeability was determined by lactulose/mannitol absorption. The venous effluent was sampled for endotoxin, potassium, bacteria, and pH every hour and urine was collected for six hours. Lactulose absorption was significantly higher in all of the experimental groups. There was increased permeability in the 60 and 90 minute groups which correlated significantly with time. Venous endotoxin, potassium, and blood cultures for bacteria did not change significantly. The pH was significantly lower every hour for six hours in the 90 minute group. These data suggest that intestinal permeability is increased with supraceliac aortic clamping and can be kept to a minimum for clamp times of under one hour.


Unilateral carotid stenosis and impaired cerebral hemispheric vascular reserve. Single photon emission computed tomography (SPECT) scanning with 99TcHMPAO (Ceretec) was used to demonstrate regional cerebral blood flow (rCBF) in sixteen patients with hemodynamically significant unilateral carotid stenosis. All patients were demonstrated by cerebral computed tomography to be without cerebral infarction. When dysautoregulation was induced by intravenous acetazolamide, eight patients demonstrated a perfusion defect ipsilateral to carotid stenosis. Repeat SPECT scanning with dysautoregulation following carotid endarterectomy showed improved or normal cerebral perfusion in seven of these patients. The results suggest that a hemodynamic mechanism for cerebral ischemic events, including transient ischemic attacks (TIA) may be more common than previously suspected. Carotid disobliteration usually improves ipsilateral cerebrovascular reserve in patients with a preoperative perfusion defect.


Hemodynamic effects of primary closure versus patch angioplasty of the carotid artery. This study evaluated the hemodynamic changes associated with patch angioplasty compared to primary closure of the canine carotid artery. A standard arteriotomy was closed either primarily, with a 5x28 mm expanded polytetrafluoroethylene (ePTFE) patch, or with a 10x28 mm ePTFE patch. Measurements for the primary closure group showed a systolic pressure gradient of 17 mmHg across the closure and a peak systolic velocity increase of 58% at mid-closure compared to proximal inflows. Flow turbulence increased at mid-closure in the 10 mm patch group, with the percent spectral window lowered from 0.50 to 0.36. These data show that primary vessel closure creates a mild local stenosis with flow acceleration but no flow turbulence. No significant hemodynamic disturbances are caused by a moderate sized patch; however, a large patch relative to native vessel dimensions creates marked flow disturbances throughout the cardiac cycle. As turbulence and flow separation are felt to contribute to restenosis, care should be taken in the selection of patch size when used following carotid endarterectomy.


Lingual infarction: a review of the literature. Lingual infarction, although a very rare entity has been reported in 16 cases since 1961. The goal of this article is to alert the physician to the symptoms of tongue claudication to prevent the morbid effects of tongue infarction and blindness due to cranial arteritis. A discussion of the disease and the differential diagnosis is included.


Surgical repair of a celiac axis aneurysm and renal oncocytoma: a single case report. Visceral artery aneurysms are unusual lesions. However the frequency of diagnosis has increased in recent years as a result of increased utilization of arteriogram and computed tomographic (CT) scan. When diagnosed in conjunction with other syndromes, alternative treatment options can be utilized. The present case discusses a 67-year-old black male who presented with a right renal mass and celiac artery aneurysm. The renal mass was diagnosed as an oncocytoma. This unique anatomy enabled us to perform a right nephrectomy in conjunction with a celiac artery aneurysmectomy with primary anastomosis between the right renal artery and common hepatic artery. This case demonstrates our approach to an unusual problem.


Hypertension due to an aneurysm of the left renal artery in a patient with neurofibromatosis. Arterial lesions in patients with neurofibromatosis are rarely described and in most cases are stenotic. The aneurysmal changes reported in the literature are usually characterized by multiple microaneurysms due to the dysplastic lesions of the artery. We report a case of a single aneurysm of the inferior hilar branch of the left renal artery of a young female with neurofibromatosis. The patient showed hypoperfusion of the renal pole fed by this branch and was hypertensive. The aneurysm had a diameter of 4 cm and showed the histological findings typical of dysplastic lesions of neurofibromatosis. The hypertension and the renal pole hypoperfusion recovered after surgical excision of the aneurysm and end-to-end anastomosis of the hilar branch stumps.


False aneurysm of the abdominal aorta due to Brucella suis. A 48-year-old man presented with a fissured false aneurysms of the abdominal aorta due to Brucella suis. Clinical findings were lumbosciatic pain, fever, and sudation. Diagnosis was reached through abdominal computed tomographic (CT) scan and arteriograms. An extremely large false aneurysm, thrombosed and perforated posteriorly, was found in the infrarenal aorta. Semiurgent therapy consisted of resection of the aneurysm and prosthetic Dacron graft replacement associated with a transposed omental wrap. Antibiotic therapy was administered for three months. Although bacteriologic specimens were negative, brucellosis was diagnosed because of a positive Wright test and high Brucella antibodies in this patient originating from an endemic area. Six months after surgery he is apparently in good health.


Infective aneurysm of the popliteal artery due to Salmonella enteritidis. Infected aneurysms of the popliteal artery are rare and Salmonella enteritidis infection in this site has not been previously reported. In the case reported herein, septic thrombophlebitis was found to be in contact with the aneurysm. Preoperative diagnosis was made through arteriography, computed tomographic (CT) scan, and positive blood cultures. The infected aneurysm was treated by resection without any reconstruction while phlebitis was treated by thrombectomy. Appropriate antibiotic therapy was administered. The patient made an uneventful recovery.


Enhanced surgical exposure for the high extracranial internal carotid artery. The need for enhanced surgical exposure for the high extracranial (Zone III) internal carotid artery is not uncommon. In certain circumstances, the posterior border and angle of the mandible may interfere with access to the distal internal carotid artery (ICA). The use of modified mandibular osteotomies has provided vascular surgeons in our institution with improved exposure of the ICA in selected cases. The intraoral sagittal split and extraoral vertical ramus osteotomies of the mandible allow manipulation of the posterior border and angle of the mandible with low morbidity and minimal postoperative complications. These procedures can be performed for both dentate and edentulous patients without the need for intermaxillary fixation. This paper introduces these modifications and discusses the benefits over previously described methods of mandibular manipulation.


Endothelial cell seeding: a review.

Endothelial cell seeding: a review. The concept of endothelial cell seeding, designed to provide vascular grafts with a nonthrombogenic lining, has progressed from crude animal experiments during the past two decades to detailed in vitro functional studies using human cells. Although favorable results have been obtained in animal studies this has yet to be translated to humans, where current application of these techniques has been limited to a very few clinical trials. The history, current status and future directions are reviewed herein.


The impact of nausea and vomiting upon quality of life measures. The measurement of quality of life in cancer patients has achieved prominence in recent years. This results from recognition of the limitations of available therapies and a clearer view of the goals of treatment in patients whose diseases may not be curable. Many different approaches to the measurement of quality of life have been proposed and these will be reviewed. In a recent survey of available methods, the Medical Research Council's Working Party on Quality of Life Measurement systematically analysed available instruments for measuring quality of life specifically in cancer patients and commented on a number of instruments of general purpose that may be used in oncology. It was concluded that no instrument is entirely satisfactory for all purposes and that available instruments have to be selected carefully for a particular study or a particular aspect of clinical practice. However, among the existing instruments, the Rotterdam Symptom Checklist for a general assessment of many facets of quality of life and the Hospital Anxiety and Depression Scale, for detecting psychosocial morbidity quickly and easily, were useful. In our own studies we have used a multiple linear analogue scale system to measure aspects of quality of life in breast cancer patients and have recently addressed the determinants of overall quality of life. Our studies identify the importance of evaluating the psychometric properties of measurement instruments in quality of life. Reliability and validity and the ability to discriminate changes with time and between clinically distinct groups have to be carefully assessed.(ABSTRACT TRUNCATED AT 250 WORDS)


Neuropharmacology of emesis in relation to clinical response. 5-HT3 receptor antagonists such as ondansetron, granisetron, ICS205-930 and zacopride are highly effective in the ferret, cat or dog to prevent emesis caused by cisplatin and other chemotherapeutic agents, and radiation treatment. The anti-emetic effects may be mediated centrally in the area postrema and associated structures of the emetic reflex such as the nucleus tractus solitarius, which have a very high density of 5-HT3 receptors. Additional sites of action may be found on the 5-HT3 receptors located on the vagus nerve or enteric neuronal elements in the gastro-intestinal tract. The precise site(s) and mechanism(s) of action of different cytotoxic treatments to induce emesis remains to be determined, but appears to involve a common action on a 5-HT3 system. The 5-HT3 receptor antagonists do not impair normal behaviour and, in particular, fail to affect the extrapyramidal motor system and do not cause sedation. Of potential benefit, the 5-HT3 receptor antagonists have an anxiolytic profile of action in rodent and primate models. The 5-HT3 receptor antagonists are revealed as an important group of drugs to prevent emesis induced by a wide range of cytotoxic treatments.


Nausea and vomiting and cancer patients' quality of life: a discussion of Professor Selby's paper. It is evident from the data presented above that nausea and vomiting are frequent side effects which are often persistent and distressing to patients. Evidence suggests, and intuitively it appears that avoidance of nausea and vomiting is important to the patients' ability to maintain their quality of life during the treatment period. It is of particular interest to note that in the literature reviewed in this paper standard antiemetic prescribing and practice were followed. It would, therefore, appear that available antiemetic agents are not always effective or may not be adequately employed. The toxicities associated with dopamine receptor antagonists, the current standard of antiemetic regimens, limit their usefulness in the clinical setting. In fact, the contribution of antiemetic therapy toxicities to the incidence of anxiety, fatigue, and restlessness which were commonly reported by patients in the studies reviewed should be considered. Additional effort to characterise the impact of nausea and vomiting on cancer patients' quality of life is needed. Clearly, the data available suggest that these symptoms should be included as part of the physical domain component of quality of life instruments used in cancer patients. Ideally, the instrument used should contain separate items for nausea and vomiting. Major side effects of antiemetic therapy should also be assessed since these may be as debilitating as the effects of nausea and vomiting. Increased awareness of total patient impact of emesis and antiemetic therapy will serve as an impetus for improvements in antiemetic therapy strategies and practices.


Antiemetic study design: desirable objectives, stratifications and analyses. Once the optimal dose and safety of an antiemetic has been established a randomised double blind parallel subjects design is recommended for phase III studies. Randomisation distributes the unknown prognostic variables so that their effects can be allowed for in tests for statistical significance. Stratification can equally distribute the known prognostic factors e.g. prior exposure to chemotherapy, strength of the emetic stimulus, age, sex and prior alcohol consumption. A cross-over design is often proposed because less patients would be required to achieve the same power as a parallel subjects study. The major problem with this design is in being able to estimate and allow for carry over effects or treatment period interactions which can interact with each other and the direct treatment effect. The study must be large enough to detect a statistically significant difference of clinical importance. Interim analyses should be preplanned and early termination should require a difference between the arms with a more significant P value than 0.05. Simple evaluation of efficacy could include quantitation of objective parameters and use of simple ordinal scales to record more subjective phenomena. In a parallel subjects design patients must assess their overall tolerance of therapy which balances the antiemetic's efficacy and toxicity.


Methodology and assessment in clinical anti-emetic research: a meta-analysis of outcome parameters. There have been major clinical advances in the control of chemotherapy-induced nausea and emesis. These advances were achieved partly by the introduction of new anti-emetic agents but important improvement came from the use of existing agents in ways developed from the results of studies based on new approaches and methods in anti-emetic research. By developing basic research tools, improving methodology and applying psychometrically sound assessments better management or chemotherapy-induced nausea and vomiting has been achieved. The goals of anti-emetic assessment are discussed here along with data and examples of assessment techniques for emesis and nausea. Examination of 153 separate anti-emetic studies between the years of 1975 and 1988 showed that emesis was the most common outcome measure used and that approximately 1 out of five studies measured some other type of outcome usually in the context of nausea and emesis. The frequency of outcome events was most commonly the dimension assessed. Examination of size of the effect of an anti-emetic regimen for these anti-emetic studies showed it to be independent of the type of outcome measured, but to be quite dependent on how the outcome was quantified. For instance, differences in the frequency or incidence of either nausea or emesis were generally larger than measurements made of the duration of either of these.


Autonomic changes during cancer chemotherapy induced nausea and emesis. Certain autonomic variables have been shown to be responsive to motion induced nausea and vomiting. Here we report preliminary data on changes in heart rate, blood volume pulse, pallor and skin temperature assessed during a one hour period at baseline, a one hour period of peak nausea, and a one hour period of emesis in five female patients receiving identical cancer chemotherapy and antiemetic drugs according to a common protocol. Examination of coefficients of variation showed that heart rate and face temperature were more stable measures across each of the three time periods than blood volume pulse and pallor. Furthermore, the four measures were found to be more variable during times of emesis than times of nausea. The four measures were shown to be responsive to patient reported nausea and vomiting. Temperature and pallor showed a linear change from baseline to nausea to vomiting. Heart rate and blood volume pulse significantly decreased from baseline time during nausea and then significantly increased from a time of nausea to during emesis. Variations in the time course of each variable change during nausea supported a view that nausea may be more related to a rebound of parasympathetic activity than a slow decrease of sympathetic activity. Replication with larger samples is needed. Examination of the nausea and vomiting of pregnancy, general anaesthesia or different chemotherapeutic agents could help explore whether results reported here are singular or representative of a more generalisable autonomic response associated with patient reported nausea.


Behavioural factors influencing the development and expression of chemotherapy induced side effects. Aversive side effects are commonly associated with potentially curative chemotherapy treatments. Despite the advances in the development and testing of antiemetic medication, nausea and vomiting remain prevalent and troublesome side effects of chemotherapy. Four studies (from 1978-1990) of 2,499 consecutive cancer patients being treated with a variety of chemotherapy agents showed that 62-72% were experiencing posttreatment nausea/vomiting despite the use of available antiemetic medication. In addition to occurring during, or up until days following, treatment with cytotoxic drugs, nausea and vomiting may begin to occur in anticipation of chemotherapy treatments. This phenomenon is called anticipatory nausea and vomiting (ANV) and it occurs in at least one in four patients. Randomised clinical trials have shown that antiemetic drugs do not control ANV once it has developed. No single clinical or patient variable has been found to be as significantly associated with the development of ANV as several in concert. We have examined the predictive value of eight clinical characteristics in a series of three clinical trials. The first of these trials was developmental; the other two have been longitudinal prospective trials. The eight clinical characteristics appear stronger in predicting those patients who will not subsequently develop ANV rather than those who will. Anxiety has been proposed as a mechanism in the development and expression of anticipatory side effects. Here we show an association (P < .05) between patient self-report of anxiety on the State-Trait Anxiety Inventory (STAI) and the Symptom Checklist-90 (SCL-90) assessed at the first chemotherapy treatment, and subsequent development of anticipatory side effects within the first five treatments.(ABSTRACT TRUNCATED AT 250 WORDS)


Economic evaluation of ondansetron: preliminary analysis using clinical trial data prior to price setting. This study combines secondary analysis of efficacy and side-effect data from a randomised controlled trial with estimates of resource use to evaluate the likely economic effects of the new antiemetic agent ondansetron. Costs, effects and cost-effectiveness of ondansetron in the prophylaxis of acute nausea and vomiting induced by chemotherapy are assessed relative to antiemetic therapy with metoclopramide. Superior efficacy of ondansetron is quantified both in terms of significant emesis avoided and emesis management costs avoided. A simple cost analysis, with the metoclopramide dosage priced at 10 pounds, indicates that therapy with ondansetron would give equivalent net treatment costs, at a price ratio (ondansetron/metoclopramide) of 2.3 to 1. If therapeutic success is defined as the avoidance of emesis and antiemetic side-effects, then the two therapies would be equally cost-effective at a drug price ratio of 5 to 1. We conclude that, (i) economic evaluation prior to price setting is feasible and informative; (ii) such models can indicate prospective data collection priorities.


Issues in the measurement of nausea.

Issues in the measurement of nausea. Measurement of nausea is essential for the evaluation of efficacy of antiemetic treatment. Frequency, duration and intensity of nausea should be assessed in all trials. Three different methods: a discrete scale (DS), a visual analogue scale (VAS) and a continuous chromatic analogue scale (ACCS) of measuring nausea and four different dimensions maximal intensity, (MI); entity, (E); duration, (D) and quantity, (Q) were evaluated in 849 cancer patients undergoing chemotherapy. A substantial agreement between the different scales was found and no advantage was shown for using an analogue (VAS) rather than a discrete (DS) scale. There was a trend towards increasing sensitivity in detecting differences as the dimension of nausea used encompassed wider aspects of this symptom (Q more sensitive than E more sensitive than MI).


Mental health. Ethical standards and human rights. In an earlier article in Nursing Standard (1), the author discussed the use of control and restraint techniques when dealing with violent or potentially violent situations. Here, he offers a nurse's perspective on the ethical and human rights issues which confront staff who are trying to cope with the challenging behaviours of their patients and who, as a last resort, may have to use physical restraint to prevent injury occurring. In intervening physically, nurses, he argues, must be aware of the legal and ethical boundaries of their practice.


Ensuring compliance with drug regimens.

Ensuring compliance with drug regimens. This article explores the difficulties patients encounter in complying with prescribed drug regimens, and describes some of the compliance aids which are commonly available. A sensitive understanding of patients' individual difficulties by health care staff is an essential precursor to successful compliance behaviour.


Abortion: the nurse's responsibilities.

Abortion: the nurse's responsibilities. Previous Royal College of Nursing guidance in relation to nurses and abortion was issued in December 1980. Since then, there have been changes in the law and new drugs for use in the termination of pregnancy have become available. The RCN has received requests for guidance from nurses in relation to their legal and moral position in caring for women who are undergoing a termination of pregnancy.


Women, nursing and caring: the issues.

Women, nursing and caring: the issues. This is the first of three consecutive articles in Nursing Standard dealing with the issues affecting women in nursing. Articles two and three will focus on the specific problems faced by black and ethnic minority women, and on the future of nurse education in relation to recruitment and retention of nurses. This week, the general issues linking women, caring and nursing are examined, and some possible explanations of why so many women are found in nursing are offered.


Patient complaints: guidance for nurses. In response to the debate at RCN Congress in 1990, the College has produced the following guidelines for good practice on handling complaints about care, treatment and services. These guidelines have been written to help nurses, midwives and health visitors to handle complaints in ways which are fair to patients and in which they feel confident. The principles are readily applicable to other disciplines and an effective complaints procedure can only be established on a multidisciplinary basis. They may be used and adapted to form local policies and should be considered in conjunction with the recommendations of the Association of Community Health Councils and government recommendations and proposals to improve patients' satisfaction and confidence in health care services.


Cystic fibrosis: managing nutrition.

Cystic fibrosis: managing nutrition. A crucial part of the management of patients with cystic fibrosis is ensuring that dietary requirements are met, and therefore weight gain and growth are achieved. The author outlines the nutritional problems faced by this client group and suggests how they may be overcome. She argues that optimum nutrition contributes not only to an improved standard of health, but also to the overall quality of life of patients with cystic fibrosis.


Interpretation of a normal chest X-ray.

Interpretation of a normal chest X-ray. Thousands of chest X-rays are taken every day in hospitals throughout the county, but what indications suggest that a chest X-ray is 'normal'? This article, written by two radiologists, offers a step-by-step guide on how to interpret the normal chest X-ray, and will assist nurses in evaluating the significance of this common diagnostic test.


Pre-operative shaving in gynaecology.

Pre-operative shaving in gynaecology. The authors describe a small scale study conducted to examine the practice of pre-operative shaving in women undergoing gynaecological surgery. The results show that the practice of shaving was not uniform among the wards surveyed and that there were differences in the method used, area shaved and times at which the patient was shaved. Recommendations for practice are suggested.


Differing approaches to nursing care.

Differing approaches to nursing care. There are many different models and frameworks for the delivery of nursing care. While there is no single 'right' way of organising the nursing service, it is important that nurses understand the various theories and systems that exist.


Nursing people with psychosomatic illness. Nursing and medical staff can feel frustrated in their attempts to help patients with problems of a psychosomatic nature. Lack of success can also compound the patient's problems, making the prospect of effective treatment even less likely. The author considers the assessment of such patients in hospital, and looks at short and long term nursing interventions as well as the therapeutic goals that can be appropriate.


A study of two "quick-and-easy" methods of assessing individual differences in student learning. A study is reported which examined the reliability and validity of two measures of individual differences in learning, a short form of the Approaches to Studying Inventory (Entwistle and Ramsden, 1983) and the Learning Style Inventory (Kolb, 1976). Both of these are short and easy to administer, making them attractive for use in the classroom. The Approaches to Studying Inventory was found to be a potentially useful measure: the predicted factors emerged, the scales were moderately reliable and those students adopting a deep approach to learning were more likely to be successful in their exams. The Learning Style Inventory, on the other hand, was relatively unreliable and the underlying factor structure did not correspond to what was predicted; there was, however, a correlation between scores on the active/passive dimension and academic success. It is concluded that the short form of the Approaches to Studying Inventory has some potential in assessing the learning styles of students, but that further refinement is required before it is adopted for general use.


Some observations in the figure drawings of clumsy children. This paper presents two exploratory studies of figure drawing by clumsy children. In the first, the drawings of 42 such children and controls, matched pairwise on chronological age and verbal IQ, were compared. Not only were the impaired children's drawings found to be generally delayed but there was also a suggestion that some fell further behind their peers as they got older. In a follow up study of a subset of the clumsy group it was found that increasing delay was indeed characteristic of some children, but others improved. In spite of improvement in some aspects of figure representation, however, the children's poor motor control persisted.


Re-examining repeated testing and teacher effects in a remedial mathematics course. This study examined the impact of repeated testing and teachers' effects on student achievement in a remedial mathematics course. A 2 x 2 completely randomised factorial design was used, with final examination performance the dependent variable and testing attempts and the teacher factor the independent variables. The study found no main effects for teacher but a main effect for testing attempts and a teacher-factor/testing-attempt interaction. Post hoc findings qualified a direct interpretation of the main effect. The implications for further research and application are discussed, giving special attention to teacher effects, the needs of remedial mathematics instruction, and the claims of mastery-learning pedagogies.


Social and academic treatments in mixed-ethnic classes and change in student self-concept. The efficacy of three pedagogical strategies for the enhancement of student academic and social self-concept in mixed-ethnic classes was examined among 594 Israeli children of varying status levels in their first year of junior high school. One treatment approach involved cooperative learning in small groups; a second approach employed a specially designed social relations programme; and the third approach presented the social relations programme and cooperative learning. A comparison group using traditional pedagogical approaches was also investigated. Status level was defined according to student sociometric standing and academic standing. Results indicated that low-achieving students of Middle Eastern background only in the comparison group sustained a significant negative change in their social and academic self-concepts. All three treatment strategies succeeded in curbing this decline. Findings were in the same direction when status was defined by sociometric standing. These results suggest that under proper pedagogical conditions minority children in mixed-ethnic classes need not suffer any decline in their self-concept.


Handwriting and spelling: dyslexic children's abilities compared with children of the same chronological age and younger children of the same spelling level. Handwriting speed and spelling were examined in a group of 10-year-old dyslexic children compared with children of the same age and with younger children of the same spelling level. The children wrote lists of words onto a digitizer pad in three different condition: a dictation, copying from a sheet on the desk and copying from a wall chart. The words ranged in complexity from simple monosyllabic phoneme to grapheme words to words needing orthographic and morphological information and non-words. There were differences in writing speed between the 10-year-olds and 8-year-olds in most conditions. There were no significant differences in speed of writing or pausing between the dyslexic children and the 10-year-olds. There was a difference in the number of errors in the spelling of non-words, the dyslexic children being inferior to both the other groups. The only difference between the dyslexic children and the 8-year-olds was in speed of writing in copying from the desk and in writing complex words. The performance of the dyslexic group was more similar to that of the 8-year-olds in the dictation but to the 10-year-olds in the copying conditions. Independent judges had no difficulty in identifying the 10-year-olds' writing but confused that of the 8-year-olds with the dyslexic children's. It is proposed that the dyslexic children had automatised movement patterns linked to spelling equivalent to their same age peers but that these patterns were built on accumulated inaccuracies in both letter formation and spelling.


Season of birth and school attendance.

Season of birth and school attendance. Previous research has shown that summer compared to autumn or spring born children have been found to do less well educationally, to be more likely to have their abilities underestimated and to be considered to have behaviour problems, but not to differ in terms of school attendance. That last result is refuted by the results of this study which is based on more than 5000 pupils in their last year of primary education and which reveals that: (a) after controlling for gender and size of family, the summer born have the poorest and the autumn born the highest attendance rates; and (b) in the case of pupils with attendance rates of 80 per cent or less, more of them are summer born and fewer, autumn born.


Special needs and the distribution of attainment in the National Curriculum. The assessment model adopted by the British Government for the reporting of attainment on the National Curriculum at the ages of 7, 11, 14 and 16 is examined, with particular reference to the nature of the levels defined. The rate of increase of spread of attainment within the cohort over time is shown to be of critical importance, particularly with respect to low-attaining students. A technique for deriving estimates of rates of spread from the norms provided with standardised tests is presented, and the estimates are found to be greater than the estimates of rate of increase of spread used in the formulation of the National Curriculum. Implications with respect to the current legal framework are drawn.


Head injured children and education: a need for greater delineation and understanding. There is continuing professional misunderstanding within education and psychology regarding the effects of head injury upon the immature brain. Children who sustain repeated mild, or single severe head injuries in falls, road accidents, or as victims of physical abuse, may look good but perform badly. There is no acceptable evidence that such children achieve a good or full recovery. Conclusions about good prognosis cannot be substantiated in the present state of inadequate assessment including the perpetual reliance on inadequate or inappropriate global estimates, such as IQ, or Glasgow Outcome scores. The basis of many problems for head injured children within education is the apparent failure to adequately delineate the variables of mechanism and severity of injury, age at insult and time since injury.


Some normative data on the Bender Gestalt test performance of Iranian children. The Bender Gestalt test of visuomotor coordination was applied to a sample of Iranian children (N = 1,600) aged between 6.0 years and 10 years and 11 months attending grades 1 through 5 of 16 public primary schools in Shiraz city, southern Iran. The administration of the test and its scoring followed the standard procedures recommended by Koppitz. The reliability of the test in its new context was investigated through readministering it to a group of 60 children after four weeks, the r being .77. The validity of the test was established by comparing scores of children at different age levels and by correlating test results with marks obtained in two sets of examinations, results of Goodenough Harris Draw-A-Person Test and indices of parental education and occupation. The results are mostly in the expected direction and indicate that the Bender Gestalt test may be used as a simple measure of cognitive-intellectual development in Iran. Observed differences between Iranian norms and those of Koppitz (1963, 1975) for American children are briefly discussed and explained.


Increased urine neopterin levels in psoriasis. The production of neopterin closely reflects activation of T-lymphocyte-mediated immunity. Oxidized and reduced forms of urine neopterin were measured by reversed-phase ion-pair high-performance liquid chromatography in patients with moderate to severe chronic plaque psoriasis (n = 40), and in a heterogeneous group of patients (n = 14) with cutaneous T-cell malignancies (CTCM). Results were compared with healthy non-psoriatic control subjects (n = 30). Neopterin levels were repeated after a course of ultraviolet B therapy (UVB) plus topical tar or dithranol, or photochemotherapy (PUVA), in 12 psoriatic patients. Fully oxidized urine neopterin levels and neopterin/creatinine ratios were significantly elevated in the psoriatic group compared with controls (P < 0.002, P < 0.05) but not in the CTCM group. Both neopterin and its creatinine ratio were significantly reduced by treatment (P < 0.05, P < 0.01). Psoriasis area and severity index scores (PASI) correlated strongly with urine neopterin levels (P < 0.001). These findings indicate that urine neopterin concentrations may be a marker of psoriatic disease activity, and further support the importance of activated T lymphocytes in the pathogenesis of psoriasis.


T lymphocytes bearing the gamma delta T-cell receptor: a study in normal human skin and pathological skin conditions. The aims of this study were to investigate the presence of gamma delta T cells in normal human skin, and the possible role of these cells in cutaneous reactions. Twenty-eight samples of normal skin from various sites, and 52 biopsies from inflammatory and neoplastic skin conditions were investigated by immunohistochemical techniques. In normal human skin gamma delta T cells were infrequently seen in the epidermis and dermis. In the inflammatory and neoplastic dermatoses, gamma delta T cells were occasionally present, accounting for 0-5% of CD3+ cells in most of the biopsies examined. In one case of pityriasis lichenoides chronica and one case of lichen planus gamma delta T cells were found to be increased, accounting for 15% of the CD3+ cells in each case. Dermal gamma delta T cells were markedly increased in three of six cases of Langerhans cell histiocytosis, with up to 30% of dermal CD3+ cells showing positive staining to an anti-T-cell receptor gamma delta monoclonal antibody. In two of these cases gamma delta T cells were seen in both the dermis and the epidermis. In two further cases dermal gamma delta T cells were not a prominent feature, but small clusters of epidermal gamma delta T cells were observed. T cells bearing the gamma delta T-cell receptor are thus not a major feature of normal human epidermis, unlike the murine system, where the great majority of epidermal lymphocytes express the gamma delta T-cell receptor.(ABSTRACT TRUNCATED AT 250 WORDS)


Aberrant expression of p53 tumour-suppressor protein in non-melanoma skin cancer. Expression of the cellular p53 tumour-suppressor protein was examined in 78 epidermal tumours, including basal and squamous cell carcinomas, keratoacanthomas, solar keratoses, Bowen's disease and viral warts. An immunohistochemical study was employed using the antibody CM-1, raised against recombinant human p53 protein. Positive staining for p53, not detectable in normal cells because wild-type p53 is rapidly degraded, reflects abnormal stabilization of p53 protein, and in many cases suggests p53 gene mutation. p53 immunoreactivity was not observed in normal skin or in viral warts. In contrast, positive staining for CM-1 was seen throughout the tumour in the majority of basal and squamous cell carcinomas and in Bowen's disease. Immunoreactivity to p53 was also observed in the majority of keratoacanthomas and solar keratoses, but was confirmed to areas of dysplastic basal epithelium. This study demonstrates that accumulation of p53 protein, suggestive in many cases of p53 gene mutation and hence loss of tumour-suppressor function, may occur as an important early step in the development of diverse epidermal cancers.


Functional assessment of the stratum corneum under the influence of oral aromatic retinoid (etretinate) in guinea-pigs and humans. Comparison with topical retinoic acid treatment. Clinically we have noted that the skin of patients treated with long-term oral etretinate becomes uniformly soft and smooth to touch, like facial skin that becomes smoother and less wrinkled following treatment with topical tretinoin. This suggests that retinoids, whether used systemically or topically, alter the physical properties of the skin, particularly of the stratum corneum (SC). To study the influence of retinoids on the SC, we serially assessed the functional properties of the SC non-invasively in retinoid-treated humans and experimental animals. SC hydration and barrier function were assessed by measurement of high-frequency conductance and transepidermal water loss (TEWL), respectively. Daily application of topical retinoic acid creams was found to rapidly induce a time- and dose-dependent, linear increase in SC hydration of the forearm skin of healthy adults over a 2-week period and to compromise its water barrier function in a similar fashion. Systemic administration of high-dosage etretinate, 4 or 8 mg/kg/day, to guinea-pigs also induced dose-dependent increases in both SC hydration and TEWL measured on the plantar skin after 1 month. Moreover, in the animals given etretinate 4 mg/kg/day we confirmed a slight but significant decrease in the number of cell layers of the plantar SC. Likewise, patients with various dermatoses began to show similar functional changes of the SC in the uninvolved skin of the flexor surface of the forearms 3 weeks after the start of oral etretinate treatment, consisting of 50 mg daily for 2 weeks, followed by gradual dose tapering.(ABSTRACT TRUNCATED AT 250 WORDS)


Humoral responses to Malassezia furfur serovars A, B and C in normal individuals of various ages. A transferable solid-phase (TSP) ELISA was developed for the determination of antibody titres specific to Malassezia furfur serovars A, B and C in human sera. A survey of levels of class-specific antibodies (IgM, IgG and IgA) to M. furfur serovars A, B and C in relation to age (2-64 years; 60 individuals) demonstrated that individuals had immunity to M. furfur by the age of 2-3 years. There was no difference in either IgM or IgG levels into adulthood. The only age-related differences were lower IgM titres to the three serovars in the 60-64 year age-group compared with younger individuals. There was, however, a difference between titres of antibody specific to the three serovars. The mean reciprocal log2 IgM titre to serovar A (6.9) was significantly higher (P < 0.05) than that to serovar B (mean reciprocal log2 titre of 5.8), but not to serovar C (6.1). In contrast, the mean reciprocal log2 IgG titre to serovar A (6.5) was significantly lower (P < 0.05) than those to serovars B and C (mean reciprocal log2 titre of 8.9 in both cases).


Variation in the deposition of the antibodies at different anatomical sites in linear IgA disease of adults and chronic bullous disease of childhood. The diagnosis of linear IgA disease of adults (LAD) and chronic bullous disease of childhood (CBDC) relies upon finding a linear band of IgA at the basement membrane zone on direct immunofluorescence. This study examines the regional variation in antigen expression in the skin of affected individuals. Direct immunofluorescence was performed on biopsies from four different sites in 17 patients with these diseases. In two patients a biopsy from the volar surface of the forearm was negative, but other sites were positive; in the remaining patients there was no variation in antibody expression with site. It is therefore recommended that, if a single diagnostic biopsy is to be taken, the volar surface of the forearm is avoided.


Information leaflets in the dermatology out-patient waiting area. Patients' attitudes to the supply and quality of information provided about their condition were examined by questionnaire before (n = 852) and after exposure to an information leaflet campaign (n = 560) in the dermatology out-patient waiting area. A high expectation of this service was demonstrated, particularly from patients under 60 years of age with chronic diseases. A variety of information sources, other than doctors, were identified which could be improved (video-systems, specialist nurses, leaflets, posters). The campaign significantly increased the percentage of patients who derived information from the leaflet source (5.6-18.8%, P < 0.001) and it reduced a demand for leaflets (16.4-9.1%, P < 0.001). However, the campaign did not alter patients' perceived need to spend more time with a dermatologist. In order to achieve a greater impact on patient satisfaction, a combination of information sources in the out-patient department should be targeted at young adults with chronic diseases.


Contact hypersensitivity to topical corticosteroids. Topical corticosteroids are increasingly recognized as relatively common contact sensitizers. Between July 1988 and December 1991 2687 patients undergoing routine patch testing were also tested with tixocortol pivalate (TP). Over the same time period 528 patients were selected for testing with a series of 18 steroids. One-hundred and thirty-one cases (4.9%) of corticosteroid hypersensitivity were detected and 119 (90.8%) of these cases were positive to TP. Thirty-seven patients reacted to one or more steroids in the steroid series, the most frequent sensitizers being hydrocortisone, budesonide (3.6%) and hydrocortisone 17-butyrate (2.5%). Of these 37 cases, 20 (54%) reacted to more than one steroid simultaneously, but the patterns of cross-reaction were not consistent with previously suggested groupings. Screening for steroid allergy should be performed as part of standard patch testing. The value of TP as a marker of corticosteroid hypersensitivity is reinforced by this study, but no satisfactory marker was found for the 9.2% of cases not detected by TP. There remains a need for further markers of corticosteroid hypersensitivity. A prevalence of 4.9% of corticosteroid allergy amongst our patients suggests that the frequency of this finding is generally underestimated.


Sustained renal function loss in psoriasis patients after withdrawal of low-dose cyclosporin therapy. Eight patients with psoriasis received low-dose cyclosporin (CyA) treatment for an average period of 12 months (range 4-16 months). There was great variability in minimal effective CyA dose. In 50% of the patients long-term treatment was limited by dose reductions necessitated by side-effects. A considerable impairment of renal function during CyA therapy was found. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured with 125I-iothalamate and 131I-hippuran, respectively. Both at the end of the active treatment period (GFR-CyA and ERPF-CyA), and 4 months after withdrawal of CyA (GFR-4mo and ERPF-4mo), there was sustained renal impairment: GFR-BL = 97 (64-117), GFR-CyA reduction 17.8% (2.2-31.9%) [P < 0.02], GFR-4mo reduction = 9.8% (5.5-21.5%) ml/min/1.73 m2 (P < 0.05 vs. BL); ERPF-BL = 401 (232-607), ERPF-CyA reduction = 10.1% (7.4-27.3%) [P < 0.05], ERPF-4mo reduction = 13.5% (3.0-32.9%) ml/min/1.73 m2 (P < 0.02). Further studies of the effects on renal function during, and after, long-term therapy of psoriasis with low-dose CyA are warranted.


Treatment of psoriasis with a 311-nm UVB lamp. In a left-right comparative study, the Philips TL-01 sunlamp, a new UVB fluorescent lamp, was evaluated in 15 patients with symmetrical psoriasis. One half of the body was treated in a cabin containing TL-01 lamps, and the other half in a cabin containing TL-12 lamps. The patients were treated three times/week, and the study was conducted in a randomized, double-blind fashion. The percentage response of psoriatic lesions was determined on the tenth and twentieth exposures. The therapeutic effect of the TL-01 lamps was superior to that of the TL-12 lamps, and treatment was better tolerated, particularly with regard to episodes of burning. This new lamp appears to provide more effective and safer phototherapy for psoriasis.


Treatment of cutaneous lupus erythematosus with acitretin and hydroxychloroquine. A randomized, double-blind, multicentre study was performed to compare the efficacy of acitretin (50 mg/day) with hydroxychloroquine (400 mg/day) in 28 and 30 patients, respectively, suffering from cutaneous lupus erythematosus (LE). The study was carried out over an 8-week period. Improvement of facial LE lesions after treatment with acitretin and hydroxychloroquine was assessed using several clinical parameters. In the acitretin group there was marked improvement or clearing of erythema in 10/24 patients (42%), of infiltration in 15/24 (63%) and of scaling/hyperkeratosis in 12/20 (60%). In the hydroxychloroquine group there was complete clearing or marked improvement of erythema in 17/25 patients (68%), of infiltration in 17/25 (68%) and of scaling/hyperkeratosis in 15/23 (65%). Overall improvement occurred in 13/28 patients (46%) treated with acitretin and in 15/30 patients (50%) with hydroxychloroquine. The incidence of side-effects was higher in the acitretin group, and necessitated discontinuation of treatment in four patients. The present results demonstrate that both acitretin and hydroxychloroquine provide effective treatment in approximately 50% of cases of cutaneous LE.


Coexistent cutaneous T-cell lymphoma and B-cell chronic lymphocytic leukaemia. Three patients with cutaneous T-cell lymphoma (CTCL) are reported who had concurrent B-cell chronic lymphocytic leukaemia (B-CLL). The separate lineage and clonal nature of the individual lymphoid malignancies were confirmed by gene-rearrangement analysis. The chronology of the illnesses did not support the hypothesis that CTCL predisposes to the development of B-cell proliferative disorders. There was no clear association with immunosuppressive therapy, and HTLV-1 studies were negative in all patients. Consequently, we speculate that a lymphoid stem cell defect, which may lead to the development of either aberrant B- or T-cell clones, may be responsible for such cases of dual lymphoid neoplasia.


Oral etoposide in the treatment of cutaneous large-cell lymphomas. A preliminary report of four cases. The favourable results of oral etoposide as single-agent therapy in four patients with a cutaneous lymphoma other than mycosis fungoides are reported. In all cases other chemotherapeutic options were limited because of prior chemotherapy or the age of the patients. Therapy with etoposide resulted in an initial complete remission in all patients, and was associated with minimal side-effects.


Recurrent neutrophilic eccrine hidradenitis. Neutrophilic eccrine hidradenitis (NEH) is a neutrophilic dermatosis primarily affecting the eccrine glands, and most commonly seen in patients undergoing chemotherapy for treatment of a malignancy. Rapid diagnosis may avert unnecessary changes in therapy to treat conditions which clinically mimic NEH. We describe a patient who developed NEH on three separate occasions provoked by two different chemotherapeutic agents--cytarabine and mitoxantrone. The lesions were morphologically distinct and differed in their anatomical distribution during each episode. The response to intravenous corticosteroids was dramatic, but lesions recurred after their withdrawal. This case illustrates the potential diversity of clinical lesions in a single patient with NEH, and its response to systemically administered corticosteroids.


Erythropoietic protoporphyria, transfusion therapy and liver disease. A 28-year-old man who had suffered from erythropoietic protoporphyria since infancy was referred because of worsening photosensitivity. Conventional therapy with beta-carotene, terfenadine and topical sunscreens was ineffective or not tolerated, and he was treated with transfusions of washed packed cells. Unexpectedly, his photosensitivity deteriorated further, his whole blood protoporphyrin levels doubled and he developed abnormal liver function tests. This is the first report of such an adverse response to blood transfusion therapy for erythropoietic protoporphyria and may have been related to subclinical hepatitis or the increased iron load associated with blood transfusion.


A case of Sweet's syndrome and myelodysplasia: response to cyclosporin. A case of severe Sweet's syndrome associated with myelodysplasia is reported. The skin lesions responded to high doses of systemic steroids, but recurred rapidly on dose reduction. Treatment with a low dose of cyclosporin resulted in sustained clearance of the skin lesions, and was associated with a stable haemoglobin level, without the need for further blood transfusions.


Neurofibromatosis of the vulva.

Neurofibromatosis of the vulva. Neurofibromatosis can be very variable in its expression. A case of neurofibromatosis presenting with vulval lesions is described.


Developmentally regulated expression of a mitogen-activated protein kinase in Xenopus laevis. Mitogen-activated protein (MAP) kinases are activated in somatic cells in response to many extracellular stimuli and in oocytes during meiotic maturation. We have examined the tissue specificity of expression of a MAP kinase (Xp42) in adult and larval Xenopus laevis. MAP kinase RNA and protein were abundant in the nervous system and lymphoid tissues and were readily detected in most other organs. A remarkably high level of RNA was detected in ovary. Fractionation of oocytes showed that MAP kinase RNA is expressed at the highest level in small oocytes, suggesting that it is a maternal RNA that is stored for early embryogenesis. The levels of MAP kinase RNA and protein did not change from the time of fertilization through to late blastula. The results are consistent with functions for MAP kinases in signal transduction in embryonic as well as adult cells.


Platelet-derived growth factor potentiates phorbol ester-induced neuronal differentiation of human neuroblastoma cells. Previous studies have shown that platelet-derived growth factor (PDGF) and PDGF receptors are expressed in the mammalian central nervous system and that primary cultured neuroblasts from rat hindbrain have functional PDGF beta-receptors. Here, it is shown that cultured human neuroblastoma cells express PDGF alpha- and beta-receptors, but not PDGF-A and PDGF-B chain mRNA. In contrast to alpha-receptor expression, beta-receptor expression appears to be associated with a mature neuronal phenotype. Under serum-free growth conditions, PDGF-AA and -BB induce a trophic and weak mitogenic response in SH-SY5Y neuroblastoma cells, showing that the PDGF receptors in these cells are functional. In combination with 12-O-tetradecanoylphorbol-13-acetate, all three PDGF isoforms induce sympathetic neuronal differentiation of the SH-SY5Y cells, as shown by morphology and by increased expression of the genes coding for growth-associated protein 43 and neuropeptide tyrosine, respectively. This indicates a potential role for PDGF in the development of sympathetic neurons in particular and of the nervous system in general.


The gene for the rat heat-shock cognate, hsc70, can suppress oncogene-mediated transformation. In cells transformed by mutant mouse p53 plus ras, the former protein is found to be complexed with the heat-shock protein cognate hsc70. To determine whether hsc70 can directly affect neoplastic transformation, nonestablished rat embryo fibroblasts (REF) were transfected with rat genomic hsc70 DNA in conjunction with various oncogenes. We report here that the hsc70 gene could efficiently suppress focus induction by mutant p53 plus ras, as well as by myc plus ras. No inhibitory effect of hsc70 was detectable in assays monitoring the ability of REF to be immortalized by mutant p53, arguing against a nonspecific deleterious effect of the hsc70 genomic clone on REF survival and proliferation. Lines generated in the presence of the hsc70 plasmid produced augmented levels of hsc70. Plasmids encoding only short NH2-terminal fragments of hsc70 could also, in some cases, partially reduce oncogene-mediated focus formation. However, a maximal inhibitory effect required the production of a functional hsc70 protein. The data presented here raise the possibility that hsc70 may be directly involved in the modulation of oncogene-mediated transformation.


Staurosporine overrides checkpoints for mitotic onset in BHK cells. Under normal conditions, mammalian cells will not initiate mitosis in the presence of either unreplicated or damaged DNA. We report here that staurosporine, a tumor promoter and potent protein kinase inhibitor, can uncouple mitosis from the completion of DNA replication and override DNA damage-induced G2 delay. Syrian hamster (BHK) fibroblasts that were arrested in S phase underwent premature mitosis at concentrations as low as 1 ng/ml, with maximum activity seen at 50 ng/ml. Histone H1 kinase activity was increased to approximately one-half the level found in normal mitotic cells. Inhibition of protein synthesis during staurosporine treatment blocked premature mitosis and suppressed the increase in histone H1 kinase activity. In asynchronously growing cells, staurosporine transiently increased the mitotic index and histone H1 kinase activity but did not induce S phase cells to undergo premature mitosis, indicating a requirement for S phase arrest. Staurosporine also bypassed the cell cycle checkpoint that prevents the onset of mitosis in the presence of damaged DNA. The delay in mitotic onset resulting from gamma radiation was reduced when irradiation was followed immediately by exposure to 50 ng/ml of staurosporine. These findings indicate that inhibition of protein phosphorylation by staurosporine can override two important checkpoints for the initiation of mitosis in BHK cells.


Effect of epidermal growth factor/transforming growth factor alpha and transforming growth factor beta 1 on growth in vitro of rat urinary bladder carcinoma cells. The response to growth factor stimulation was evaluated in clonally derived rat bladder carcinoma cell lines, ranging from nontumorigenic to tumorigenic and metastatic, in athymic nude mice. In the nontumorigenic cell line D44c, epidermal growth factor (EGF)/transforming growth factor (TGF) alpha weakly stimulated anchorage-dependent, but not -independent, growth. In tumorigenic/nonmetastatic cells (G1-200 Cl-17), EGF/TGF-alpha stimulated markedly anchorage-independent, but marginally anchorage-dependent growth, whereas TGF-beta 1 inhibited anchorage-independent growth and DNA synthesis. In the highly tumorigenic/metastatic cell line LMC19, EGF/TGF-alpha stimulated anchorage-dependent growth weakly and anchorage-independent growth strongly. In these cells, TGF-beta 1 did not inhibit anchorage-independent growth and DNA synthesis but increased the size of colonies irrespective of the presence of EGF, and some cells were scattered around colonies in soft agar. None of the cell lines showed evidence of TGF-alpha-specific mRNA transcription. Expression of TGF-beta 1 mRNA increased in parallel to the biological aggressiveness of the cell lines. Highly tumorigenic and metastatic cells also demonstrated gelatinase activity involving 72 kilodalton and 92 kilodalton types. Our data suggest that the growth-stimulatory effect of EGF/TGF-alpha in soft agar may be limited to cells that are already tumorigenic and that EGF/TGF-alpha is not effective in making nontumorigenic cells become tumorigenic (or in making nontumorigenic cells grow in soft agar).(ABSTRACT TRUNCATED AT 250 WORDS)


Ca(2+)-regulated serine protease associated with the nuclear scaffold. The nuclear scaffold (NS) is a proteinaceous network of orthogonally arrayed intermediate filament proteins, termed lamins, which is responsible for nuclear structure. Recent work has demonstrated that a subset of lamins A/C is proteolytically cleaved to produce an ATP-binding protein. This proteolytic cleavage is accomplished by a NS protease activity, which shows a considerable selectivity for lamins A/C and is stringently regulated by Ca2+ in vitro, suggesting that it might also participate in control of NS breakdown in various scenarios. Here, we identify the major NS protease as a novel serine protease with a predominantly chymotryptic-like substrate preference, and we show that even transient perturbations in cytosolic Ca2+ have significant effects on the NS protease activity. This NS protease activity shows extensive similarities to the multicatalytic proteinase complex. In addition to a potential role in control of NS breakdown at mitosis and/or under pathological conditions, this NS protease is also strategically located for other functions, such as inactivation of various oncogenic proteins or maturation-promoting factor.


Germ-line splicing mutation of the p53 gene in a cancer-prone family. Li-Fraumeni syndrome is a rare autosomal dominant susceptibility to a variety of cancers including carcinomas of the breast and the adrenal cortex, tumors of brain and muscle tissue, and leukemias. Affected individuals develop cancer at a young age and often at multiple primary sites. A study has been conducted into the genetic basis of cancer in a particular Li-Fraumeni syndrome family. Examination of p53 as a candidate susceptibility gene revealed that, in two affected individuals, there was an aberrant larger transcript of 3.6 kilobases present in both tumor and constitutional material in addition to the normal-sized 2.8-kilobase transcript. The additional transcript was not found in three unaffected family members. S1 nuclease mapping localized the insertion toward the 5' end of the p53 transcript near exons 4 and 5, and sequencing revealed a point mutation in the splice donor site of intron 4 in the germ-line of the two affected individuals, which accounted for the presence of the larger transcript. The same splicing mutation was also detected in two obligate carriers and was not found in two unaffected individuals. As no mutations were detected in exons 5-8 in either tumor examined, the second p53 allele was most likely lost during tumorigenesis in both tumors. The demonstration of a germ-line splicing mutation in affected individuals from a Li-Fraumeni syndrome family provides for a novel mechanism of p53 inactivation not seen previously in other affected families, in whom the mutations have all been missense.(ABSTRACT TRUNCATED AT 250 WORDS)


Differential effects of phorbol esters on proliferation and calcyclin expression in human endometrial carcinoma cells. Calcyclin is a member of the S-100 family of calcium-binding proteins, whose expression is enhanced when quiescent cells are exposed to mitogenic signals. The function of calcyclin is unknown, but it is thought to be involved in modulating the intracellular calcium concentration following mitogenic stimuli. Since activation of protein kinase C (PKC) also occurs following stimulation of quiescent cells by a variety of mitogens, we have investigated the relationship between calcyclin expression and PKC activation in three human endometrial adenocarcinoma cell lines. The addition of 10(-7) M 4 beta-phorbol 12-myristate 13-acetate (PMA) to HEC-50 and HEC-1B cell cultures resulted in a change in cell morphology, an inhibition of proliferation, an increase in calcyclin transcription rate, and an increase in calcyclin mRNA and calcyclin protein levels. In contrast, PMA had no effect on cell morphology or cell proliferation in the Ishikawa adenocarcinoma cell line but enhanced calcyclin expression. Another bioactive phorbol ester had the same effect, whereas the calcium ionophore A23187 and the non-phorbol-ester-type tumor promoter thapsigargin had no effect on calcyclin expression. The effect of PMA on calcyclin expression was blocked by the simultaneous addition of the PKC inhibitor staurosporine and by protein synthesis inhibition with cycloheximide. RNase protection assays and primer extension analysis demonstrated that PMA enhanced transcription from all three of the previously identified transcription start sites in the calcyclin gene. These data clearly demonstrate a dissociation between calcyclin expression and cellular proliferation and suggest that the enhanced calcyclin expression which is seen in quiescent cells following mitogenic stimuli may result from activation of the PKC system.


Erosive gastritis and portal hypertension. There is conflicting evidence concerning the effects of portal hypertension on the gastric mucosa. This paper summarises the histological and haemodynamic alterations which are present in both human and experimental portal hypertension. Despite the fact that histological studies suggests that the gastric mucosa is an oedematous plethoric structure in portal hypertension, haemodynamic studies show that gastric mucosal blood glow is at least maintained if not increased in portal hypertension. The term "active" rather than "passive" congestion is a more appropriate description of the basic change present in the gastric mucosa in portal hypertension.


Primary bile duct stones and bacterial activity. The results of this study suggest that infection with beta-glucuronidase active bacteria is the initial event in the nucleation of primary bile duct stones (PBDS). PBDS from five patients were morphologically fragile and "earthy" with alternating light and dark brown pigment layers with no evidence of a distinct central nucleus that may have been reminiscent of a different structure. Chemically, calcium bilirubinate and calcium palmitate were prominent throughout their structure. All bile duct biles had a positive culture and were always associated with at least one bacterial species which was beta-glucuronidase active. Moreover, fragments of PBDS nuclear areas had positive cultures that were comparable with those present in their individual bile duct bile. Microscopic examination of bile showed abundant precipitation of calcium bilirubinate granules in all samples. Thus, bile duct bile infection with beta-glucuronidase active bacteria (e.g. E. coli, C. perfringens) appears to be a key factor in PBDS pathogenesis, having a precursor role, rather than being a consequence. Bile stasis is likely to be a co-factor which must have a supportive role in subsequent stone growth.


Standard surgical approaches to primary choledocholithiasis--definitive versus temporary decompression. The occurrence of retained/recurrent calculi after primary CBDE followed by temporary T-tube decompression, have remained at rates varying from 5.4% to 20.9% over the last 10 years in spite of sophisticated pre and intraoperative imaging techniques. It is postulated that a functional obstruction, due to dysmotility of the SO, lies behind most stone-containing ducts. Thus it seems logical to us that a permanent "fenestration" should be the management of most such ducts. We prospectively followed-up, for one to 10 years, two groups of patients submitted to primary CBDE aiming to assess the short and long-term results of two different surgical approaches to duct lithiasis. In one (Group A) 162 CBDE's were performed, out of 680 CHE's (24%), with a "positivity" of 68% and in the other (Group B) 80 CBDE's, out of 438 CHE's (18%), with a "positivity" of 70%. In Group A a T-tube decompression was used in 79(49%) and a definitive drainage in 83(51%) whereas in Group B the T-tube was employed in only 3(4%) and some form of permanent "fenestration" in 77(96%). There were no significant differences between the operative mortality rates, which were 2.5% in Group A (1 death post T-tube, 3 post CDJ) and 1.3% in Group B (1 death post CDD). The long-term results, though, were significantly worse among patients of Group A whose ducts were temporarily decompressed: 10/79 (12.7%) required further aggressive interventional therapy for retained/recurrent stones while only 3.8% (3/80) in Group A and 1.3% (1/76) in Group B required revisional surgery for bilio-digestive anastomotic complications with cholangitis. It is concluded that it is against the long-term efficiency of the approach utilized in Group B that the new laparoscopic techniques should be compared.


Left-sided hepatectomy with a linear stapling device: an experimental study on pigs. Thirteen pigs underwent resection of the left liver lobe. By random selection, the animals were resected either with the aid of an RLG 90R linear stapling device or by the conventional finger-fracture technique. There was one postoperative death due to anaesthetic complications. The median operative time using the stapler was 27 min (range 19-40 min) which was significantly shorter (p = 0.0065) than that required for resection by the finger-fracture technique (42.5 min; range 37-55 min). The median blood loss, estimated by counting the number of gauze swabs used, was 425 ml and 275 ml for the finger-fracture resected and stapler resected groups, respectively (ranges 275-550 ml versus 175-300 ml; p = 0.015). The animals were sacrificed and examined one week after the operative procedure. Except for a small bile pseudo-cyst in one pig operated upon with conventional resection, no sign of bleeding or biliary leakage was revealed. This study demonstrates the feasibility of stapling the liver to facilitate resection.


Diagnosis and surgical treatment of hepatic hydatid disease. In this report two hundred and twenty six patients with hydatid disease were admitted to the Surgical Department of Erciyes University (Kayseri) and Sişli Etfal Hospital (Istanbul) between 1978 and 1990 and reviewed retrospectively. One hundred and two patients (45.1%) were male and 124 (54.9%) female. In the patients with hydatid cysts the most frequent symptom was right upper abdominal pain (66%). The most frequent signs were hepatomegaly (43.8%) and palpable mass (39%). One hundred and sixty seven patients (73.9%) were examined with ultrasonography which has a diagnostic value of 94%. Preoperative complications were infection of cyst (7%), intrabiliary rupture (3.5%) and anaphylactic shock (0.4%). All patients were operated on by using various surgical techniques; omentoplasty (101), external drainage of residual cavity (64), marsupialization (25), capitonnage (15), introflexion (10), pericystectomy (6), and hepatic resection (5). The main postoperative complications were wound infection (12%) and biliary fistula (2.6%). The total mortality rate was 1.8% in this series.


A comparison of SMS 201-995 and oesophageal tamponade in the control of acute variceal haemorrhage. Forty endoscopically proven active variceal bleeds were entered in a prospective trial comparing oesophageal tamponade with SMS 201-995 infusion. Oesophageal tamponade controlled 19 of 20 bleeds over the first four hours and 14 of 18 bleeds over 48 hours. SMS 201-995 infusion controlled 18 of 20 bleeds over the first four hours and 10 of 20 bleeds over 48 hours (p = 0.15). No significant differences between the groups were seen in time to control of bleeding, amount of blood transfused or number of patients crossed over to the opposite treatment. Complications in the oesophageal tamponade group were discomfort due to the tube (17 patients) and chest infection (10 patients), while in the SMS 201-995 group 7 chest infections and one episode of hyperglycaemia occurred, with no symptomatic complaints. The patient survived the admission in 15 of the oesophageal tamponade bleeds and all of the SMS 201-995 bleeds (p = 0.047). An intravenous infusion of SMS 201-995 appears to have comparable efficacy to oesophageal tamponade in variceal bleeding.


[Cell fine structures observed by scanning electron microscopy]. The scanning electron microscope (SEM) provides vivid seemingly three dimensional images which are easier to understand for us than transmission electron microscopic images. For this point of view scanning electron microscopy is advantageous in morphological researches of cell fine structures. Nevertheless, there were few studies in this field, because SEM had much lower resolution than transmission electron microscope (TEM) and because there was no adequate method to reveal intracellular structures. In recent years, however, the resolution of SEM has been markedly improved and the specimen preparation techniques have also advanced. In this paper, some of our preparation technique for revealing cell surface structures or intracellular structures, in particular, osmium-DMSO-osmium method, and the results observed by these methods were described. 1) Nucleus. The nucleus was wrapped with a nuclear envelope that consisted of two membranes enclosing a narrow space. On the surface of the envelope many nuclear pores were observed. 2) Endoplasmic reticulum (ER). Rough ER consisted of flattened cisternae, arranged in parallel. The surface were studded with many ribosomes which were often arranged spirally to form polysomes. Smooth ER consisted of tubules. 3) Golgi complex. a) The Golgi stacks were all linked by anastomosing. b) Connection between Golgi stacks and rough ER was often observed. c) Cisternae in a Golgi stack were connected each other. 4) Mitochondria. The mitochondrion was bounded by 2 sheets of unit membrane and the inner membrane projected into the interior of the organelles to make mitochondrial cristae.


Use of human leukocyte antigen-mismatched allogeneic lymphokine-activated killer cells and interleukin-2 in the adoptive immunotherapy of patients with malignancies. Clinical effects and side effects were investigated in the adoptive immunotherapy of patients bearing malignant diseases using human leukocyte antigen (HLA)-mismatched allogeneic lymphokine-activated killer (LAK) cells. Allogeneic LAK cells were induced from peripheral blood lymphocytes (PBL) of healthy donors with the same blood types as those of patients. Recently we succeeded in increasing the proliferation rate and enhancing the cytotoxic activity of LAK cells by means of initial stimulation with pokeweed mitogen (PWM, PWM-LAK cells). Five of 12 patients applied in the adoptive immunotherapy showed clinical effects such as partial or complete regression of pulmonary metastases and pleural effusion. All pulmonary metastatic lesions were eliminated in one case by this adoptive immunotherapy combined with chemotherapy. Toxic effects were chillness, fever and general fatigue which were reversible, and no allergic side effects occurred even though allogeneic LAK cells were injected frequently. In the patients who received more than 10(11) of allogeneic LAK cells, anti-HLA class I antibodies appeared without any evidence of autoantibody. However, immunological side effects were never experienced after injection of allogeneic LAK cells even when the anti-HLA class I antibodies existed in the patients; this phenomenon suggests the safety of the adoptive immunotherapy using allogeneic LAK cells. Taken together, allogeneic LAK cells could be considered as alternative therapy for patients with malignancies who could not supply sufficient materials of autologous LAK cells. Recently, LAK cells, particularly PWM-LAK cells were found to obtain significantly potent and prompt lectin-dependent cell-mediated cytotoxicity (LDCC). All tumor cells confluent in microtest plate well could be annihilated by PWM-LAK cells plus PWM less than 8 hours. New immunotherapy using PWM-LAK cells or lectin-stimulated LAK cells with PWM or other lectins is discussed.


[Augmentation of therapeutic effect of adoptive immunotherapy through a synergy between transferred killer cells and host's fresh lymphocytes]. Among several approaches to augment the therapeutic effect of adoptive immunotherapy, we focused the antitumor synergy between transferred killer cells and host's fresh lymphocytes. Immunotherapy models using murine tumors or clinical experiments revealed that preadministration of immunostimulator such as OK-432, followed by chemotherapeutic agents such as cyclophosphamide, can induce host's non-cytotoxic fresh lymphocytes that act synergistically with cultured killer cells against autologous tumor cells. Immuno-chemo-lymphocytotherapy (a sequential treatment with OK-432, chemotherapy and adoptive immunotherapy) is useful to treat the patients with advanced cancer even if the number of transferred lymphocytes is limited.


[Expansion of peripheral blood lymphocytes by culture with immobilized anti-CD3 antibody and IL-2]. Peripheral blood lymphocytes separated from about 20ml of blood were cultured with immobilized anti-CD3 antibody and IL-2. Total T lymphocytes in the culture expanded about 2,000 times by 2 weeks culture. Expanded T lymphocytes were infused to cancer patients, and safety and feasibility was confirmed. This method will be applicable for prevention of cancer recurrence.