THE LITTLEWOOD FAMILY – 1995

1995  February. Holiday Property Bond at Buckland Court in Cotswolds with Katie and Jim

img_3105Photos: Walks along parts of the Cotswold way. Top right: HPB Buckland court

We went for walks on various sections of the Cotswold Way. Also there were interesting shops along the main street in the nearby town of Broadway. 

1995 February 3rd – 4th. Jim visits Anil and Gita Mehta at Dundee University               As Chair of the Research and Medical Advisory Committee I accompany Dr Martin Scoot, the CFT Scientific Director, on a visit to Dundee University to discuss the CFT patient Database. The new database is organised by Dr Anil Mehta and his wife Gita  Anil is a paediatricians with a strong scientific research background and Gita is into science and computers This was a routine visit and in view of the distance we stayed in Dundee overnight.

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Gita Mehta
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Anil Mehta

I only mention this particular visit because of an incident related to the train journey from York to Dundee.  During the meeting at the University, we were in a modern laboratory type office with various exposed pipes and ducts as is common in modern buildings. I thought  I could hear a constant hissing noise. I asked Anil what the hissing noise was – was it the central heating? But no one else could hear the noise!  I realised it was tinnitus which I have had ever since that day. I’m quite sure it was caused by barometric damage sustained on our train journey to Dundee. Two trains passed at high speed causing the windows of our carriage to suddenly to move slightly. I’m sure that was when my ears were damaged.

Martin Scott and I enjoyed our periodic visits to Dundee. The meetings were good and interesting and we often went to and excellent curry restaurant with the Mehta’s.  We stayed at a pleasant hotel, the Shaftesbury, where one could have Arbroath Smokies for breakfast.

Erika Sims
Dr Erika Sims

The Mehtas were responsible for the early development of the patient database. The early years were not easy. Consultants at the various hospital caring for children with CF were busy and many were reluctant and slow to submit their data. However matters slowly improved particular when we linked to submission of data to the small grants each clinic received from the CF Trust!  Eventually the CF Trust took over the database and started using Port CF as id the CF Foundation. The present CF Patient Registry is a very efficient data base run by a team of professionals providing very accurate annual data on the over 10,000 patients in the UK.     However some very useful data was produced while the Mehtas were running the data base which eventually formed the basis for a number of useful publications relating to neonatal CF screening – many were authored by a scientist Dr Erika Sims. Erika went on to have a successful career in science and medical research in the University of East Anglia.

–  Sims EJ, Green MW, Mehta A.   Decreased lung function in female but not male subjects with established cystic fibrosis-related diabetes.  Diabetes Care. 2005 Jul;28(7):1581-7
–  Sims EJ, McCormick J, Mehta G, Mehta A; Steering Committee of the UK Cystic Fibrosis Database.   Neonatal screening for cystic fibrosis is beneficial even in the context of modern treatment. J Pediatr. 2005 Sep;147(3 Suppl):S42-6
–  McCormick J, Ogston SA, Sims EJ, Mehta A.J Cyst Fibros.   Asians with cystic fibrosis in the UK have worse disease outcomes than clinic matched white homozygous delta F508 controls.2005 Mar;4(1):53-8.
–  McCormick J, Sims EJ, Green MW, Mehta G, Culross F, Mehta A.  Comparative analysis of Cystic Fibrosis Registry data from the UK with USA, France and Australasia. J Cyst Fibros. 2005 May;4(2):115-22.
–   McCormick J, Sims EJ, Mehta A. Delayed diagnosis of females with respiratory presentation of cystic fibrosis did not segregate with poorer clinical outcome. J Clin Epidemiol. 2006 Mar;59(3):315-22.
–  Mehta G, Sims EJ, Culross F, McCormick JD, Mehta A. Potential benefits of the UK Cystic Fibrosis Database. J R Soc Med. 2004;97 Suppl 44(Suppl 44):60-71

1995  February. Sarah and Richard’s Wedding Anniversary

Simon Seat S and R anniv 26.2.1995We went for a walk to Simon’s Seat in the Yorkshire Dales.
Simon’s Seat is the prominent summit on the western edge of Barden Fell in North Yorkshire. It is the largest of several rocky outcrops on the moor. 

With its rocky summit Simon’s Seat overlooks Skyredale and dominates the skyline above the village of Appletreewick just off the side of lower Wharfedale.

In the upper photo Sarah and Richard can just be seen in the valley through which one walks to access the path over the moor to the summit.

During the weekend we also went for dinner at Woodhall where Richard and Sarah had their wedding reception.

1995 March 15th. London for  a routine meeting at CF Trust headquarters in London Road Bromley

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Headquarters in London Road Bromley. An excellent building provided by the first Chairman and founder Joe Levy (Google Earth)

I include this item as it was a journey I (and often with Ann) was to make every week or two until I retired from the CF Trust in 2011. In the early years, when I was still working at St James’s, I would catch 7.20 am train from Leeds to London usually with breakfast on train (used to be good kippers); arrive Kings Cross, take the tube to Victoria then train to Bromley then walk half a mile to CF Trust which was on London Rd Bromley. Then, after the meeting, back to Kings Cross by same route to catch evening train from Kings Cross to Leeds and finally drive home from Leeds station. I used to work on the train. Over the years it became increasingly hard work and I was pleased to retire as Chairman in 2011 at the age of 79 years. Ann was invaluable in arranging all my trips and a good help during these journeys and in later years came with me on most trips. 

The building shown was donated to the CF Trust by the first Chairman Joe Levy. In recent years it was decided that it was too far out of central London and the headquarters moved to 1 Aldgate, London  – where the rent was £250, 000 per year!

1995 February 20th – 22nd. Examining in the Membership exams at the Royal College of Physicians in London.

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Royal College of Physicians London.

This was the only time I examined in the MRCP in London and I have never been asked to examine in Edinburgh. It was quite an interesting experience but I avoided being involved in future. Some colleagues seemed to enjoy examining and the college activities but I would rather do a clinic!    The current College building itself is notable. It was designed by architect Sir Denys Lasdun, opening in 1964 and has since been recognised as a building of national importance: it is a Grade I listed building, one of a very select band of post-war buildings sharing this distinction.

1995 March 1st. London for Executive Meeting of CF Trust
This is the first mention of my attending the Executive so I must have been appointed Chairman of the Research and Medical Advisory Committee by this time having been a member from the mid-Eighties. So as Chairman I would be attending the meeting ex officio to report to the Trustees on RAMAC proceedings. I used to write a report and present it for discussion at the meeting. My main report concerned the Research Grants that had been approved, explaining them so they could be approved officially by the committee. As I became increasingly involved with the Trust I used to write a report on all my activities (and opinions!) called “Dr Littlewood’s Diary” which the Trustees seems to enjoy!!

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Swire House, Buckingham Gate, London
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Peter Levy OBE

The Trustees meeting were quite impressive. They were held in the board room at Swire House in Buckingham Gate, London.  At this time 1995 the Chairman was Peter Levy OBE, the son of Joe Levy the founder of the CF Trust. Peter, was also a distinguish London businessman,  was chairman of the CF Trust from 1987 to 1996 when he was

Duncan Bluck
Duncan Bluck CBE

succeeded by Duncan Bluck CBE. Duncan had a very distinguishedbusiness career mainly in Hong Kong and the far East. He was managing Director of Cathay Pacific and subsequently Chairman of the Swire Group. Hence we were allowed to have executive meetings in the Swire Group Offices in Buckingham Gate, London.. It was Duncan and Sir Robert Johnson who persuaded me to take over the Chairmanship of the CF Trust in 2003 – a total surprise when they approached me after one of the Trustees meetings, but I accepted with some hesitation!

March 24th. We attended a Race Meeting at Doncaster with TV interview

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Doncaster race course

One of the Trustees, John Edkins had arranged for one of the races to be sponsored to raise money for Cystic Fibrosis. Ann and I were invited to go as his guests to a party in his box – a first for us both!  As part of my duties as RAMAC chairman I had an interview with John Francome, a previous  champion jump jockey and now a sports commentator and very successful novelist. I had to climb up a tall tower from where he was

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John Francome MBE

doing his commentaries.  I arrived in his box rather breathless. “Sit down Doc I’ll be with you in a second” while he went through the runners of the next race. “Now tell us about cystic fibrosis” Which I did. He was very pleasant and I was particularly pleased to meet him as I had read all his books. So the afternoon went well and the Trust had a good deal of publicity.

Pugh Richard
Dr Richard Pugh.

A few days after this meeting I had a letter from a retired and well respected consultant paediatrician, Richard Pugh, whom I knew when he  worked in the paedaitric department in Leeds  before going to Hull as a consultant. His letter ran as follows :-  

“Dear Jim, While waiting with the other OAPs for the Monday afternoon film in back and whiteI saw your CF Trust advertisement and nearly made out a cheque!!  I must say you are a “natural” for television; relaxed, distinguished, thoughtful, considerate and logical. I suspect that when you retire in 1999(?) we shall still be on the brink of a ” cure”, but accept that much will have been achieved, and much of it by you”

March 28th. Two lectures to family doctors at Pately Bridge Playhouse

Normally would not describe a standard postgraduate lecture for I was fortunate to be invited to give a great numbe,  but these were rather different. The meeting was held at a quaint little theatre in Pateley Bridge in the Yorkshire dales near Harrogate. The building began life as a Primitive Methodist Chapel in 1859. When the Methodists united as part of a national policy in 1933, the congregation transferred to the nearby Wesleyan Chapel. After 3 years the salvation army bought the building and it was successful for some time but by the late Fifties the congregation had dwindled and the Salvation Army left. The empty building, now rotting and prone to flooding, was purchased by the Pateley Bridge Dramatic society for £125. The building was gradually restored and the society gave their first performance e there in 1968; there was refurbishment in 1995.

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Pateley Bridge –  floods in 2020

The theatre was hired out for various functions and I suspect the drug firm thatsponsored my lectures helped to support the refurbishment.   The 73 seat auditorium surrounds the stage . It was an interesting variation on th usual venue for a postgraduate lecture. My lectures were on “Cystic Fibrosis” and “Coeliac Disease”. Incidentally there was severe flooding in Pateley Bridge in 2020.

1995 March 31st-April 1st. Lecture on CF at Turnberry Golf Course
It was quite a long drive out to the coast but worth it when Ann and I eventually arrived. We stayed in the magnificent Turnberry Hotel in one of the choice front rooms with a fabulous view over the sea.  

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The Turnberry Hotel
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The Lighthouse and Ailsa

 I gave a lecture on “The Management of Cystic Fibrosis” at 9.30 am and at 2.00pm was on the first tee to start 18 holes on this magnificent course that I had seen so often on television.

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The 9th hole at Turnberry

Although I did not play particularly well I seemed to be inspired at the challenging 9th hole – the 187 yard par three across the rocky coastline.  I hit a great shot across the sea and cliffs onto the green. A local Scot spectator appeared from out of the the gorse and said “Greet Shot Sir!!” It really made my day!
In 2003, the 18th hole on the Ailsa Course, “Ailsa Hame”, was renamed “Duel in the Sun” as homage to the battle between Tom Watson and Jack Nicklaus in 1977 during the 1977 O

The course is now called “Trump Turnberry” – what a dreadful name for a beautiful course . I refuse to use the name!

April 13th. Cystic Fibrosis Trust lecture at Post House Hotel, Preston

I must have given a lecture to CF parents at most of the CF Trust branch meetings in most cities and towns in the UK over the years.  This usually took the usual form of brief business meeting for the local branch members, followed by my talk with plenty of slides, which usually lasted an hour, then questions which usually went on for a considerable time. I enjoyed these meetings and, as Chair of the Research and Medcial Advisory Committee,  it was good to get out and talk with the parents. Usually the local paediatric consultant attended; very occasionally they were a bit stroppy and resented my coming to tell them how it’s done!!  I remember on one occasion in Edinburgh giving  a fiery talk on the importance of early aggressive treatment, the distinguished and locally feared senior paediatric consultant proved quite a problem.

April 18th. To Oxford for a Gene Therapy clinical trial meeting. 

Some of the people involved in the early gene therapy meetings. From L to R Alan Cuthbert, Martin Evans, Eric Alton, Duncan Geddes, Deborah Gill, Steve Hyde, Chris Boyd , David Porteous – They are all professors and Martin Evans shared a Nobel prize in 2007 and was knighted. in 2004.

Leading scientists from Oxford, Cambridge, Edinburgh and London attended regular meeting to discuss research and clinical trials of gene therapy, the gene having been identified in 1989.  I attended in my role as Chair of RAMC; the CF Trust would be involved in funding gene therapy research.  At that time it was still hoped and believed that gene therapy would be the way ahead for specific treatment. As it turned out, although a number of studies showed that gene therapy was feasible and safe, the degree of clinical effect was disappointing.
Although CF is a multi-organ system disease, most people with CF die of progressive lung disease that begins early in childhood and is characterized by chronic bacterial infection and inflammation. Nearly 90% of people with CF have at least one copy of the ΔF508 mutation, but there are hundreds of CFTR mutations that result in a range of disease severities. A CFTR gene replacement approach would be efficacious regardless of the disease-causing mutation.

Mitchell Drumm
Mitchell Drumm

After the discovery of the CFTR gene in 1989, the in vitro proof-of-concept for gene therapy for CF was quickly established in 1990 by Mitchell Drumm and his colleagues in the USA.
Drumm ML, Pope HA, Cliff WH, Rommens JM, Marvin SA, Tsui L, Collins FS, Frizzell RA, Wilson JM. Correction of cystic fibrosis defect by retrovirus-mediated gene transfer. Cell 1990; 62:1227-1233.
In 1993, Steve Hyde, his wife Deborah Gill and others from the UK group reported successful correction of the ion transport defect in CF transgenic mice by gene therapy. Hyde SC, Gill DR, Higgins CF, Tresize AEO, MacVinish LJ, Cuthbert AW, Ratcliff R, Evans MJ, Colledge WH. Correction of ion transport defect in cystic fibrosis transgenic mice by gene therapy. Nature 1993; 362:250-255.

The history of CF gene therapy, from the discovery of the CFTR gene to current state-of-the-art gene delivery vector designs is discussed in an excellent recent article.          Cooney AL, et al, Cystic Fibrosis Gene Therapy: Looking Back, Looking Forward. Genes (Basel). 2018 Nov 7;9(11). pii: E538. doi: 10.3390/genes9110538.[PubMed]Free PMC Article 

I have reviewed the main articles on gene therapy in CF from the early Nineties and subsequently on our website cysticfibrosis.online/history/ topics/gene therapy. Certainly the topic and the funding of it was to prove an increasing responsibility of the CF Trust as I will describe later.

1995 April 22nd. Bill and Muriel Search’s Diamond Wedding party.

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Bill and Muriel Search at home in Alwoodly

IMG_3137A big luncheon party at Rudding Park, near Harrogate.  We saw Bill and Muriel frequently and they were at many of our family parties and celebrations. They were Ann’s Uncle and Aunt, Muriel being Betty’s sister; they were almost “surrogate grandparents” for our girls after their actual grandparents were no longer with us.

April 27th. Combined CF clinic at York Hospital with Dr David Beverley
I used to do combined clinics with the local consultant at a number of towns and cities in the region every 3-6 months.  David Beverley, previously our Senior Registrar at St James’s, had been appointed consultant paediatrician in York where he had a regular clinic for children with CF.  I would go to York to see a number of the patients with him in a combined clinic. We would see 5 or 6 children in the afternoon session; they would all have an up-to-date chest Xray, sputum cultures and recent blood tests available. When David was with me at St James he became very experienced in CF care.   When he was with us he coordinated an important trial comparing the new acid resistant pancreatic enzymes, Pancrease and Creon, with the standard preparation Cotazym showing the marked superiority of the two new preparations.                                                                                                              Beverley DW, Kelleher J, MacDonald A, Littlewood JM, Robinson T. Comparison of four pancreatic extracts in cystic fibrosis. Arch Dis Child 1987; 62:564-568. 

 CF Research Fellows from Leeds, Eduardo Moya, David Beverley and Ian Bowler

These mages show the new enzymes Creon and Pancrease that revolutionised the treatment of intestinal malabsorption in CF patients. The acid resistant microsphere pass through the stomach acid intact as can be seen in the sample in the petri dish retrieved from the duodenum. The table from the article shows the marked superiority of Pancrease and Creon over the standard enzymes.  The results were so impressive in improving the bowel problems one didn’t really need a trial. I recall one teenage girl telling me the new enzymes had totally revolutionised her life which previously had been restricted by her terrible bowel problems.

It was good to see David Beverley, now a successful consultant paediaitrician  in York,  running a good CF clinic with satisfied parents and healthy looking children.

1995 29th April – 10th May. To the USA to visit the CFF headquarters in Maryland and a visit to Blue Ridge Mountains
We combined a two day working visit to the headquarters of the US CF Foundation in Maryland with a holiday traveling down the Blue Ridge Mountains and into the South.

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Dr Bob Beall

As I had recently been appointed Chairman of the Research and Medcial Advisory Committee at the CF Trust, I was keen to see how the Centres Committee worked at the CF Foundation.  So I asked them if I could visit and attend one of their centre committees. Bob Beall the very effective President , Preston Campbell III  and all the staff were very welcoming and I attended the full days meeting.  

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Dr Preston Campbell III who succeeded Bob Beall as CEO and President in 2015

 My impression was that the CFF exerted much greater authority and control over the CF centres who depended heavily on them for financial support in a country with no NHS.  For example the CF centres would be visited periodically to ensure they were giving a good service; the centres committee members who made the visit would report back to the Committee. In the UK consultants were much less dependent on the CF Trust as most of their funding came from the NHS.

The visit was very interesting and I got to know many of the people who worked there. I had to admit the CFF was then, and increasingly so now in 2020, in a different financial league to the UK CF Trust. For example in 2014, the Cystic Fibrosis Foundation sold the rights to the royalties of the new modulator drugs, the development of which they had supported, for $3.3 billion, twenty times their Foundation’s 2013 budget!

After the visit to the CF Foundation we had a holiday travelling down the Blue Blue Ridge Parkway.

The parkway  runs for 469 miles (755 km) through Virginia and North Carolina mostly along the spine of the Blue Ridge a major mountain chain part of the Appalachian Mountains.   It was a very good trip with spectacular views. We saw a peregrine falcon – a transient speck flashing across the morning sky!  

Blue-RidgeMs-bear.tiffThe other animal we looked out for all the way down the Blue Ridge Mountain road was a black bear. We had no luck until our very last morning driving down the final mile or so of the central road. On our left, on the left hand side of the road, a small black bear was peering  over the grass verge. I stopped the car at once and reached for the camera by which time the bear had disappeared – that was our only sighting of a black bear! The lady at the shop at the bottom of the road said she had lived there 12 years and had never seen a bear!!!
Photo609772432924_inner_46-19-741-19-46-976-741-976After we left the Blue Mountains we stayed at some lovely Plantation Houses which did Bed & Breakfast. They had been the old plantation owners houses turned into a B&B accomodation. All were very welcoming and friendly.  Breakfast was served at  one large table so guests could chat to each other. At one the owners were also farmers. They gave us an extensive and very interesting tour of the farm.

The Jamestown settlement was our final destination. Historic Jamestown is home to the ruins of the first permanent English settlement in North America. It had been established by the Virginia Company of London as “James Fort” in May 1607. Jamestown served as the colonial capital from 1616 until 1699. includes the remains of 18th-century Ambler Mansion. Artifacts from the region’s settlers are on display in the Archaearium archaeology museum. Nearby, the Jamestown Settlement is a living-history museum with recreations of a 1610s fort and a Powhatan Indian village.  The settlement was located on the northeast bank of the James River about 2.5 miles southwest of the center of modern Williamsburg. 

Figures; The early years of the settlement.; original harbour: Williamsburg; a visitors’ tour round the reconstruction of the original settlement                                                                       There is a very detailed and interesting account of the history on Wikipedia .

1995 June 17th. Awarded an OBE in the Birthday Honours List

photoIn early May, on our return from North America, I was surprised (to put it mildly!) to open a letter from the Prime Minister’s Principal Private Secretary informing me I was to be awarded an OBE in the Birthday Honours List on June 17th.   This was a total surprise until the  moment I opened the envelope from the Mr John Major’s secretary. The award was for “Services to Medicine”.
The Honours List was published on June 17th when we were attending the annual European CF Society conference Brussels.  There were general cingratulations all round particularly from our own staff, some of whom were at the meeting.                                                                            In the Brussels photo L to R are Alison Morton (Dietitian), Ann Littlewood (Research Nurse and wife), Sunita Seal (Paediatric Research Registrar), Jim Littlewood, Sally Connelly (CF Research Fellow), a friend, Sharyn McLaughlin (Paediatric CF Nurse), Anita Watson (Adult CF physiotherapist).

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Jimmy's staff OBE

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There were more celebrations when we returned to St James’s with some more of the unit staff in my office (photo right).   Also a feature in the Yorkshire Post ! There were general congratulations from the staff at Jimmy’s who were delighted. We also had a party at home for the family. 
There were a rather surprising 126 letters of congratulation! From colleagues 60, patients and relatives 13, friends and acquaintances 23, family members 15, and interestingly 15 from official sources nursing organisations, BMA, health minister, Chief Constable, Lord mayor of Leeds, Presidents of the Royal Colleges of Paedaitrics and Child health and also the Royal College of Physicians of London, University of Leeds and Virginia Bottomley the Secretary of State for Health.

One of my favourite cards was from the children with CF who came regularly to ward 12 at St James’s for treatment. This card was managed by Vicky S.

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I will describe the visit to Buckingham Palace and our trip to London later in the year.

July 6th. Lecture on Cystic Fibrosis at Ninewells Hospital, Dundee
This was a well attended lecture organised by the CF Trust. It was memorable for a rather strange reason!! Over the previous few days I developed progressive swelling of my big toe which on the day of and during the lecture became more severe and very painful. As the pain increased during the lecture I gave an increasingly forceful lecture vigorously condemning people who did not treat CF aggressively!    Ann said it was one of the best lectures she had ever heard me give!! 

b9c16ef4a3a076eb29ff945ef905bbf6On return to Leeds I went to see a rheumatologist, Dr Martin. He took one look at the toe and diagnosed gout which settled in a few days on treatment with the anti-inflammatory he prescribed (Rheumox). At the age of 87 I still get occasional attacks but this was definitely the first and I’m afraid it was diagnosed initially by a GP colleague as osteoarthritis!  I have had gout in my heel (photo) and knee as well as the more usual site in the big toe joint.  Usually a combination of hot weather, dehydration and too much alcohol will trigger an attack.

1995 22nd July. Katie was awarded a degree at Sheffield University in Sociology and Social Policy.    

We were very proud parents and went over to Sheffield University for the degree ceremony. Katie would go on to obtain a degree in nursing and ultimately become a successful Practice Nurse in Sheffield.

1995 August. Sue and Nick moved to their present house at 12 Cliff Way, Radcliffe on Trent 

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Family lunch in the Haines’s new garden, In the foreground (L to R) Dave, Eli, Susan, Ann and Nick
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Grandma serves lunch to Lewis, Tom, Ivor , ben and Elliot

This was the first of very many happy times we have had at the Haines’s new house with its very pleasant large garden.

1995 August. Visit Sarah and Richard at 13 Amesbury Rd, Cardiff

This was our first visit to Sarah and Richard’s new house in Cardiff (photo). We also played golf at St Mary’s Golf Course and Country Club down the M4, and attended an opera evening at Dyffryn Gardens (photo).                                                                      Interesting that “two houses later” they eventually moved to a large very impressive barn conversion with extensive grounds only a short distance away in Dyffryn. Dyffryn House and Gardens are now partially restored and belong to the National Trust.

1995 September 4th. Golf CF Charity Day at Wetherby Golf Club

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Howard Wilkinson and a Barfield partner with Jim and another player

A good evening golf fund raiser followed by dinner at Wetherby. It was a financial success – I don’t remember exactly how much. I gave the customary  few words on cystic fibrosis after the dinner.  I recall the I was playing in a four ball with one of the Garfield partners and Howard Wilkinson, the Leeds United Manger – who was kind enough to retrieve my ball when I went out of bounds!!

1995 September 16th – 20th. European Respiratory Society, Barcelona

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With Ann and Ella Conway

We had a very pleasant few days in Barcelona with Steve Conway and his wife Ella. Wedid not have any work to do but attended many of the meetings.                                      

1995 Steve with S Shak in Barcelona
Jim Littlewood, Steve Shak, Steve Conway

We  were fortunate to with Steve Shak and took the opportunity of a photo. Steve is a scientist who was  responsible for producing rhDNase (Pulmozyme) – a most effective mucolytic.   Dornase alfa (proprietary name Pulmozyme) is a highly purified solution of recombinant human deoxyribonuclease I(rhDNase), an enzyme which selectively cleaves DNA. Dornase alfa hydrolyzes the DNA present in sputum/mucus of cystic fibrosispatients and reduces viscosity in the lungs, promoting improved clearance of secretions.
Shak S, Capon DJ, Hellmiss R, Marsters SA, Baker CL. Recombinant human DNase 1 reduces the viscosity of cystic fibrosis sputum. Proc Natl Acad Sci 1990; 87:9188-9192.                                                                                                              An early report of the significant effect of recombinant human DNase1 (Pulmozyme) on sputum viscosity in people with CF by Dr Steve Shak. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase) in the treatment of CF, the authors cloned, sequenced, and expressed rhDNase. Catalytic amounts of rhDNase

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A – Viscid sputum                           B- after treatment with Pulmozyme (website)
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Typical viscid CF sputum (author’s photo)

greatly reduced the viscosity of purulent CF sputum, transforming it within minutes from a non-flowing viscous gel to a flowing liquid. The reduction in viscosity is associated with a decrease in size of the DNA in the sputum. The authors suggested that inhalation of an rhDNase aerosol may be a simple direct approach that would help individuals with CF, and other patients with pneumonia or bronchitis, to clear their airways of purulent secretions

In 1950 Armstrong JB & White JC (Lancet 1950; 2:739-742) had shown that bovine pancreatic DNase1, added to viscid purulent sputum, destroyed the extra cellular fibres of DNA and reduced the viscosity.   Later Elmes PC & Armstrong JB (Thorax 1953; 8:295-300) reported its use in chronic bronchitis, but the side effects of the bovine preparation eventually precluded its use and further development at that time (Raskin P. Am Rev Respir Dis 1968; 98:697-698). In Leeds we had 10 year old girl with CF whose sputum was like glue. I explored the possibility of using bovine pancrease but the side effects were too great. I rang Margaret Hodson at the Brompton – had she any suggestions. Interestingly she said occasionally hypertonic saline inhalations helped.  We tried it and it did help. This was before hypertonic saline came into widespread use following Elkin’s 2006 study from Australia.

Undoubtedly Pulmozyme has proved to be one of the most successful therapies introduced during the past 30 years since the early Nineties. It is widely used for CF and many other respiratory conditions (now there some 359 references on Medline – nearly 200 concerning use cystic fibrosis).  By 2018 Pulmozyme was taken by 90.7% od patients on the US CF Foundation registry who were over 6 years old and over 60% on the UK Patient registry; eventually it would be used earlier and by milder affected and younger patients – for example in the UK 18.2% of children up to 3 years were taking Pulmozyme.

1995 September 21st – 24th. Lecture on Pancreatic Enzymes. Gdansk, Poland
We previously had a young girl with CF referred from Poland to Leeds. We fly to Gdansk on the Baltic coast where I had been invited to give a lecture on Pancreatic enzymes at the Polish Paedaitric Society meeting.  I started by greeting the audience in Polish – which is apparently “JEN DOBRE”! (Ann had a phrase book!!) It got the proceedings off to a good start. Everyone was very friendly.  I had already provided the text of my lecture and they had translated it into Polish. The first article I’ve ever had published in Polish! (photo).
The other interesting feature of this meeting of the Polish Paediatric Society was the conference dinner in the evening which was followed by a ladies fashion show – apparently this is usual as most of the paediatricians in Poland who attend the meeting are ladies!!

We had some time for sight seeing and Ann also went round the sights with a Polish guide while I was in the meeting.

The appearance of the rebuilt Gdansk compared with the destruction of the end of the second world war. My lecture in Polish!  Our hotel in Gdansk.   Ann on the Baltic beach. Jim by the harbour – the tall brown building with the red roof on the left in the distance is the tallest dock crane in the world. 

1995 September 29th – October 3rd. Spanish CF Society, Jerez.  Lecture on “Management of Nutrition”.
UnknownInteresting meeting held in an old monastery attached to the hotel. I kept feeling I was preaching as I gave my talk from the pulpit!  Talk went well although I had a viral infection on the way down to Jerez by coach.                                            After the meeting we had an opportunity to  look round Jerez and also the sherry manufacturing.  We saw where the sherry was made and were presented with one of the long bendy ladles used for sampling the sherry in the barrels (photo).

1995 October 11th – 21st. North American Cystic Fibrosis Conference. Dallas

1280px-Hilton_Anatole_-_Dallas_-_4393_-_jpfagerback_2013-05-04
Windham Anatole Hotel Dallas

I always looked forward to these excellent meetings. The conference was always held in a huge hotel – on this occasion the Windham Anatole in Dallas. It was a good meeting.  We had 4 posters from Leeds –
– Miles Denton & Jim Littlewood. Does treatment to reduce P. aeruginosa prevalence encourage Stenotrophamonas maltophilia?
-Sunita Seal et al. Gut transit times and fat digestion – a comparison of standard and high strength pancreatic enzymes.
Jim Littlewood et al. 20 years continuous neonatal screening one hospital. progress of the 37 patients and their families
Naresh Kumar et al. Scoloiosis in children with cystic fibrosis

I used to ensure that a number of our staff attended with a piece of research they had been involved with. I usually managed to obtain funding for them – often from a drug firm whose product we had been investigating.     There was always a good party at the conference. Managed to get Ann and Anita Watson (our adult physiotherapist) released later in the evening!!!

We had a tour round Dallas and saw the building from which Kennedy was shot and the road where he was shot. Ann visited South Fork Ranch, the home of J R Ewing. She went with Debra Gill’s mother and baby – Debra Gill is a senior scientist with the UK Gene Therapy Group whom I mentioned above. She is  married to Steve Hyde the other Oxford scientist on the Gene Therapy Consortium.

We visit Ro and Larry Serena in Maryville for a few days before moving on to the Great Smokey Mountains National Park. We knew them as they previously rented a house in Bardsey near us. They came to us for Christmas and Lary , a superb golfer, played golf with my friend Phil Coldbeck and myself at weekends.    We went boating for the day, had a pleasant meal overlooking the Pacific Ocean, and stayed in their impressive house. We have seen them periodically when travelling in the USA. Ann and Serena were good friends when they lived in England.
We move on to visit Great Smoky Mountains National Park.

1995 November 20th. To London, Flemings Hotel, for Investiture tomorrow
Sarah, Richard and Sue come to dinner in the evening; Sue and Sarah will be coming to the palace tomorrow – only two guests other than one’s partner. We had nibbles and champagne in our room and  dinner in the hotel.

The following morning we went by taxi to the Palace. The ceremony was impressive. An aide told us what would happen and it all went  well. I’m afraid I can’t remember what  the Queen said to me but I recall saying the the progress with CF was very exciting!

Lots of pictures were taken in the quadrangle of Buckingham palace.  As only two guests, other than one’s wife, could attend, Katie kindly volunteered to step aside for her sisters.

1995 November 29th. Sarah’s graduation in Bristol.

Sarah received an additional nursing qualification at a ceremony in Bristol. She was now working full time nursing in Cardiff and wrote a thesis on certain aspects of intensive care.   The impressive ceremony was in Bristol and later we had family celebrations at Sarah and Richard’s house in Cardiff with his parents Chris and Dan Evans.

 1995 December 8th – 10th. Doug and Jennifer Addy visit us in Bardsey
photoAlthough very cold weather we had a good walk round Fewston Reservoir. It was good to see our old friends again. It is undoubtedly Ann who keeps all our old relationships going and she gets on very well with Jennifer. Although Doug and I enjoy each other’s company we relay totally on our wives to keep the lines of communication open!                                   It seems a long time ago that the Addys were in Leeds and Doug was in the Leeds paediatric department. We wrote a paper together.
(Addy DP, Littlewood JM. Ventricular tachycardia associated with hyperkalemia Am J Dis Child 1969; 117:706-709).

1995 December 13th. British Thoracic Society Annual Meeting, Queen Elizabeth Centre, London

Robinson Teresa
Teresa Robinson
Gilbert John
John Gilbert

I presented a paper on the cost of home vs. hospital intravenous antibiotic therapy – a study which was funded and very professionally organised by Glaxo. Manchester data was also included.
We had published one of the first papers on home intravenous antibiotic therapy in children with CF. The first  study had been coordinated by Dr John Gilbert, our CF Research Fellow at the time, and Teresa Robinson our CF Nurse Specialist – two essential members of the CF team.

Gilbert J, Robinson T, Littlewood JM. Home intravenous antibiotic treatment in cystic fibrosis, Arch Dis Child 1988; 63(5):512-17.

This recent study showed that a 2 week course of home IV costed £1.5K and the same treatment in hospital cost £2.5K.  It was a good study and although tit was  never published in a refereed journal the abstract was quotable in the Thoracic Society proceeding of the Conference. Similar later studies came to similar conclusions.

1995 Christmas & Boxing Day in Bardsey with extended family  

                    END OF 1995