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Biomedical subjects

L M Banks

Publications and source records attributed to L M Banks.

At least 19 recordsLinked to original sources

Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis.

In a randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover over a period of 2 years. Our study comprised 117 Caucasian postmenopausal women, otherwise healthy apart from reduced bone density. They received either intranasal synthetic SCT (200 IU either three times weekly or daily) or placebo. Compared with placebo, daily intranasal calcitonin resulted in no significant bone loss in the lumbar spine, as assessed by dual photon absorptiometry, over the 2-year study period (P < 0.02). In this group, women more than 5 years postmenopause, with the lowest baseline bone mass, showed the greatest response to this treatment, with a total increase placebo in lumbar spine BMD of 3.1%. Significant spinal bone loss (P < 0.005) occurred in women receiving either placebo or thrice-weekly calcitonin. Although the rates of bone loss in the proximal femur were not significantly different in the three groups, there were differences over time. Whereas bone loss in the daily calcitonin group was insignificant, women who received placebo or thrice-weekly calcitonin experienced significant bone loss (P < 0. 001). No significant changes in biochemical markers were observed in any group. Therapy was well tolerated and there were no significant treatment-related adverse events. We conclude that intranasal SCT 200 IU daily is effective and safe for the prevention of bone loss in postmenopausal women with reduced bone mass.

Administration, Intranasal

Non-invasive measurement of microvascular permeability to a small solute in man: validation of the technique.

1. The purpose of the study was to evaluate a non-invasive technique for measurement of microvascular permeability to a small hydrophilic solute. 2. The technique measures the clearance of 99mTc-labelled diethylenetriaminepenta-acetic acid (99mTc-DTPA) from plasma into interstitial fluid in a limb after intravenous injection and uses a scintillation probe and a technique of graphical analysis called the Patlak plot, the uptake constant of which reflects 99mTc-DTPA transfer from plasma to interstitial fluid. Using deconvolution analysis, the retention function in the limb of intravenous 99mTc-DTPA was also measured. 3. The clearance values given by these two analytical techniques were compared with clearance from the same vascular bed after bolus femoral intra-arterial injection of 99mTc-DTPA. 4. Sixteen patients undergoing routine diagnostic arteriography were studied: six received sequential femoral intra-arterial injections of 99mTc-labelled human serum albumin (HSA) and 99mTc-DTPA, two received sequential intra-arterial and intravenous injections of 99mTc-HSA and eight received sequential intra-arterial and intravenous injections of 99mTc-DTPA. Tissue uptake and clearance were recorded from the limb with a scintillation probe and plasma clearance by arterial blood sampling. Tracer recirculation was addressed using a second scintillation probe over the contralateral limb. 5. After intra-arterial injection, 99mTc-HSA clearance was monoexponential, reflecting intravascular transit, and was completed by 2-5 min in seven subjects and in about 10 min in one. The corresponding 99mTc-DTPA clearance curves in the six subjects who also received intra-arterial DTPA were biexponential, analysis of which yielded a 99mTc-DTPA extraction fraction of about 0.6. By comparison with 99mTc-HSA clearance, the first exponential clearly corresponded to intravascular transit of unextracted 99mTc-DTPA. 6. In the eight patients given sequential intra-arterial and intravenous injections of 99mTc-DTPA, the second exponential recorded after intra-arterial injection, representing 99mTc-DTPA clearance from the interstitial fluid, agreed well with (a) the Patlak uptake constant recorded over the limb after intravenous injection, representing clearance from plasma into the interstitial fluid and (b) the retention function of 99mTc-DTPA in a limb calculated by deconvolution analysis. The mean clearance following intra-arterial injection (expressed in relation to extracellular fluid volume) was 9.6 (SD 2.4) ml min-1 100 ml-1, while the corresponding mean clearance after intravenous injection was 8.8 (2.1) ml min-1 100 ml-1 calculated by Patlak analysis and 10.5 (2.7) ml min-1 100 ml-1 by deconvolution analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Capillary Permeability

Holmium-YAG laser for gall stone fragmentation: an endoscopic tool.

A systematic review of the 2.1 mu holmium-YAG laser for gall stone lithotripsy was undertaken. This infrared laser, which can be used endoscopically and percutaneously, has safety advantages over other lasers and has potential as a general purpose vascular and surgical tool. Twenty nine gall stones (mean mass 1.3 g) were fragmented in vitro using pulse energies of 114 to 159 mJ/pulse at 5 Hz with a 0.6 mm fibre, while being held in an endoscopy basket. All stones were successfully fragmented, requiring an average of 566 pulses with a 5 Hz pulse repetition frequency. The number of pulses required increased with gall stone size and mass (p < 0.01), and decreased with both pulse energy (p < 0.01) and operator experience (p < 0.05). The biochemical content of the stone did not significantly affect the number of pulses needed. The potential hazard of the laser to the biliary endothelium was investigated. At the pulse energies used, five pulses at close contact penetrated into the serosa of fresh gall bladder wall. No damage was seen when two pulses were fired. This laser shows considerable promise in gall stone lithotripsy. Until further safety data are available, however, its use with endoscopic vision is advised.

Cholelithiasis

Detection of low bone mineral density by dual energy x ray absorptiometry in unsuspected suboptimally treated coeliac disease.

Patients with coeliac disease may present with calcium malabsorption but it is unclear whether this results in longterm impairment of bone mineralisation. Dual energy x ray absorptiometry (DXA) was used to study bone mineral density in 34 asymptomatic coeliac disease patients, treated with a gluten free diet for at least two years, and also in 10 newly diagnosed or untreated patients. As expected, untreated patients had low bone mineral density in all regions. In the 29 treated female coeliac disease patients, overall mean values for age adjusted bone mineral density expressed as Z scores were normal although there were many patients with low values, particularly of the lumbar spine and total body. Scores in the postmenopausal patients were significantly worse than in the premenopausal patients and low mean Z scores were found in the five treated male patients. The subjects who had reduced bone mineral density could not be predicted clinically but, despite being asymptomatic, were more likely to have subtotal or partial villous atrophy on small intestinal biopsy (p < 0.0275). In conclusion, although many treated coeliac disease patients have normal bone mineral density, suboptimally treated and newly diagnosed or untreated patients have osteopenia. To reduce the risk of osteoporotic fractures, it is recommended that bone mineral density be measured in all treated coeliac disease patients and those with osteopenia have a repeat intestinal biopsy to assess disease activity.

Absorptiometry, Photon

The use of xenon-133 for measurement of blood flow through systemic arteriovenous malformations before and after therapeutic embolization.

Embolization is increasingly used to treat systemic arteriovenous (AV) shunts although its success, as judged by either angiographic or clinical means, is difficult to quantify. The aim of the study was to quantify blood flow through AV shunts with 133Xe, which, because of its relatively long transit time through peripheral tissues, behaves like microspheres. Following arterial injection, 133Xe entering an AV shunt rapidly arrives in the lung and can be quantified with a scintillation probe. In 17 patients with systemic AV shunts, the reduction in shunt flow following therapeutic embolization was quantified in the angiography theatre by comparing the initial count rates in the lung, recorded by probe, following injection of identical quantities of 133Xe into a supplying artery before and after embolization. By comparing the lung counts with those given by an intravenous injection of 133Xe, the fraction of flow at the catheter tip entering the shunt was also quantified. Tissue perfusion in the vascular territory distal to the shunt was measured at the same time by recording the clearance of non-shunted 133Xe with a second probe over the extremity. Control injections of 133Xe were given in the contralateral limb in order to assess 133Xe transit in the absence of shunting and to compare tissue perfusion between the two sides. Shunt flow ranged from 40% to 100% (of that at the tip of the catheter) (n = 14), while the reduction in shunt flow following embolization ranged from 15% to 96% (n = 19). Tissue perfusion distal to the shunt and in the contralateral limb was about 5 ml 100 ml-1 min-1. Contrast medium had no consistent effect on tissue perfusion in either limb, or on shunt flow. There was no difference in peripheral perfusion between the abnormal and control sides, nor any significant difference in perfusion in the distal tissue on the abnormal side before and after embolization. There was, however, a consistent increase in the fraction of the injected 133Xe delivered to the distal tissue after embolization (median increase 93%, p < 0.001). The technique is relatively simple and merits further development as a means of continuous quantification of systemic AV shunt flow in the angiography theatre at the time of embolization.

Adult

Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: links between osteoporosis and cardiovascular disease?

The effect of spinal degenerative changes and aortic calcification on bone mineral density measurements was studied in 115 healthy early post-menopausal women. Lateral lumbar spine radiographs and quantitative computer tomography images were used to determine the presence and severity of aortic calcification and degenerative changes in the lumbar spine. Women with spinal degenerative calcification had higher spine bone density when measured by dual photon absorptiometry compared to those without calcification (P < 0.01), but this was not reflected by the quantitative computer tomography or the proximal femur bone densities, suggesting that spinal calcification artefactually increases spinal bone density when measured by dual photon techniques. Women with aortic calcification had significantly lower quantitative computer tomography and proximal femur bone density compared to those without calcification (both P < 0.05). These women may be at increased risk for both osteoporosis and cardiovascular disease, suggesting a common aetiological factor such as oestrogen deficiency.

Aortic Diseases

Baculovirus expression of the human papillomavirus type 16 capsid proteins: detection of L1-L2 protein complexes.

The human papillomavirus (HPV) type 16 major capsid proteins L1 and L2 have been produced in a baculovirus expression system. Both proteins are expressed at a high level and can be readily solubilized. The L1 capsid protein migrates close to its expected Mr of 60K. On the other hand L2 exhibits a much higher Mr migrating at 73K, which is considerably greater than its predicted Mr of 50K. The identity of both proteins has been confirmed also by Western blot analysis. Both proteins are produced in drastically reduced amounts in the presence of tunicamycin. In addition both L1 and L2 show interesting patterns of phosphorylation. L1 is phosphorylated only weakly and this appears to be quite labile, whereas L2 is very heavily phosphorylated and this, in contrast, appears to be very stable. We have also made use of a dual expression vector for co-expressing the L1 and L2 proteins within the same baculovirus-infected cell. The results obtained from this system demonstrate the presence of protein complexes forming between the two capsid proteins. These studies indicate that at least the initial events in capsid assembly of HPVs can occur in the absence of viral DNA.

Animals

Dietary intake of calcium and postmenopausal bone loss.

The use of calcium supplements to prevent postmenopausal bone loss and hence osteoporosis is widespread, but the evidence for their efficacy, either alone or in combination with other treatments, is contradictory. Skeletal measurements and dietary intake of calcium were determined in 59 healthy postmenopausal women, most of whom were within five years of the menopause. No correlation was found between current intake of calcium and either total calcium in the body or the density of trabecular or cortical bone in the forearm or vertebral trabecular bone. Dietary intake of calcium did not influence the rate of postmenopausal bone loss in the 54 women who completed 12 months of active or placebo treatment. Even when extremes of calcium intake were examined no difference was found in bone measurements between the women with the highest and lowest intakes. The results of this study suggest that the bone density of women in the early menopause is not influenced by current dietary intake of calcium.

Adult

Calcitonin for prevention of postmenopausal bone loss.

A 2-year randomised pilot study was conducted in 70 patients to see whether the osteoclast-inhibiting effect of calcitonin would reduce postmenopausal vertebral bone loss. An oestradiol-treated group was included in the study as a positive control since oestrogens are known to be effective. Calcitonin reduced vertebral bone loss in doses above 250 micrograms human calcitonin (50 international units) a week, and at this dose was as effective as oestradiol.

Administration, Oral

Production of antibodies of predetermined specificity against herpes simplex virus DNA polymerase and their use in characterization of the enzyme.

Peptides from preselected regions of the herpes simplex virus DNA polymerase were used to generate monospecific antisera to defined regions of the enzyme. The antisera were used to localize the polymerase within the infected cell and to determine the time of synthesis during productive infection. Comparison with a neutralizing polyclonal antiserum was used to show the specificity of the peptide antisera. By using the antisera the stabilities of the DNA polymerase, the alkaline nuclease, and the major DNA-binding protein were determined, and the state of phosphorylation of the DNA polymerase was compared with each of these proteins.

Animals

Apparent extra-hepatic invasion by metastatic tumours in the liver.

Focal changes involving the liver capsule, subjacent tumour and contiguous structures are described on computed tomography (CT) in patients with metastatic tumours in the liver. These changes were correlated with the relevant resected liver tissue which had been perfused and sliced in planes comparable to the CT slices. The capsular changes represented 'umbilication', overlying necrotic and fibrosed tumour with contiguous structures, usually the diaphragm, perihepatic fat or omentum, fixed to the liver capsule by inflammatory or organising processes, but not invaded by tumour. Localised hypodense areas on CT in the region of the capsule do not represent extracapsular spread of tumour and therapy ought to be planned accordingly.

Abdominal Neoplasms

Regional and total skeletal measurements in the early postmenopause.

In a cross-sectional study of 70 early postmenopausal women, regional bone measurements were compared with total body calcium (TBCa). Spinal and forearm trabecular bone were mainly related to age and time since menopause. In contrast, TBCa and forearm integral (cortical and trabecular) and cortical bone were unrelated to age, although the time since menopause also had some influence. Forearm integral and cortical bone measurements were quite well correlated with TBCa (r = 0.84 and 0.73, respectively, P less than 0.001). The correlation between spinal bone measurements and any of the forearm measurements, even purely trabecular bone, was weak (r less than 0.52, P less than 0.001). Our results show quite clearly that forearm bone measurements cannot be used to predict bone density in the vertebrae. Loss of ovarian function affects bone in general, and trabecular bone in particular. Bone measurements at specific anatomical sites are clearly necessary for studies of metabolic bone diseases and their response to treatment.

Adult

Vertebral CT scanning.

Quantitative CT of vertebral trabecular bone is established as a useful technique for assessing bone mass. We have developed a modified method of spinal CT which can be used on any standard third or fourth generation whole body scanner without requiring extra software or hardware. Measurements have a high precision and accuracy, with acceptable cost and radiation exposure. We have shown that our results compare favourably with those from other centres. The sensitivity of the measurements encourages the widespread clinical application of this technique.

Adult

Studies on the herpes simplex virus alkaline nuclease: detection of type-common and type-specific epitopes on the enzyme.

Five monoclonal antibodies to the alkaline nuclease of herpes simplex virus (HSV) types 1 and 2 have been used in immunoperoxidase tests to demonstrate the nuclear localization of the enzyme within HSV-1- and HSV-2-infected cells and to purify the enzyme from cells infected with either virus by immunoadsorbant chromatography. Affinity chromatography with a 32P-labelled extract of HSV-2-infected cells has enabled us to demonstrate that the nuclease eluting from the immunoadsorbant is a phosphoprotein, hence confirming the nuclease to be identical to the phosphorylated polypeptide previously referred to as ICSP 22 (HSV-2) or ICP 19 (HSV-1). In addition, the results clearly demonstrate that monoclonal antibodies Q1, CC1 and CH2 are directed against HSV type-common epitopes while V1 and T2T1 antibodies are against HSV-2-specific epitopes on the enzyme. Using the type-specific monoclonal antibodies in an immunoperoxidase test, the enzyme specified in cells infected with intertypic recombinants has been typed; correlation of these data with restriction endonuclease maps of the recombinants has enabled us to map the position of the active site of the nuclease gene to map units 0.168 to 0.184 on the genomes of both HSV-1 and HSV-2. Taken with the data mapping the mRNA encoding this enzyme, the nuclease active site can be mapped to 0.168 to 0.175 on the genome. Finally, the use of monoclonal antibodies in immunofluorescence tests on infected cells has demonstrated that the nuclease is synthesized within 2 h post-infection.

Antibodies, Monoclonal

Comparison of barium and diatrizoate bowel labelling agents in computed tomography.

A new suspension of barium sulphate, E-Z-CAT, for use as a bowel labelling agent in computed tomography (CT) of the abdomen and pelvis, has been compared with diatrizoate (Gastrografin) in 111 patients. The E-Z-CAT labelled the duodenum more efficiently and patients preferred its taste. Both substances are satisfactory bowel-labelling agents.

Barium Sulfate

Computed tomography of hilar cholangiocarcinoma: a new sign.

Thirty-seven patients with histologic proof of cholangiocarcinoma at the confluence were examined by computed tomography (CT) to determine whether this examination is of value in the assessment of these patients for surgery and whether there are any features specific to this type of tumor. Thirty-two patients showed intrahepatic duct dilatation; six of these showed dilatation of ducts in one lobe only. Eighteen patients had intrahepatic low-attenuation areas, while eight had a mass lesion in the porta hepatis. Two of the lesions in the porta hepatis and four of the low-attenuation lesions enhanced. Atrophy of a lobe was noted in seven patients. This feature is not commonly recognized and is suggestive of cholangiocarcinoma rather than other hepatic tumors. The results of this study show that CT provides useful anatomic information preoperatively but that the appearances are nonspecific. Lobar atrophy is highly suggestive of hilar cholangiocarcinoma, either of long-standing or with unilateral portal venous involvement.

Adenoma, Bile Duct

Interactions between herpes simplex virus DNA-binding proteins.

Monoclonal antibodies directed against several herpes simplex virus (HSV)-induced DNA-binding proteins were used to investigate protein interactions in HSV-infected cells. Q1 monoclonal antibody, which is specific for the HSV-induced alkaline nuclease, when used in an immunoadsorbant column resulted in the purification of the alkaline nuclease, to which large quantities of the major DNA-binding protein were bound. Conversely, when a monoclonal antibody to the major DNA-binding protein was used in affinity chromatography other polypeptides (including the DNA polymerase and alkaline nuclease) were eluted in addition to the major DNA-binding protein. Similar results were obtained when the experiment was performed using a monoclonal antibody to another HSV-2 DNA-binding protein. These results suggest the possibility that these polypeptides interact as part of the HSV DNA replication complex, and this hypothesis is discussed.

Antibodies, Monoclonal