Tuesday, August 15, 2017

Neurocysticercosis in an Orthodox Jews

ORIGINAL ARTICLE

Neurocysticercosis in an Orthodox Jewish Community in New York City

Peter M. Schantz, V.M.D., Ph.D., Anne C. Moore, M.D., Ph.D., José L. Muñoz, M.D., Barry J. Hartman, M.D., John A. Schaefer, M.D., Alan M. Aron, M.D., Deborah Persaud, M.D., Elsa Sarti, M.D., Marianna Wilson, M.S., and Ana Flisser, D.Sc.
N Engl J Med 1992; 327:692-695September 3, 1992DOI: 10.1056/NEJM199209033271004
Abstract
Article
References
Citing Articles (195)
NEUROCYSTICERCOSIS is an infection of the central nervous system with the larval forms (cysticerci) of the pork tapeworm Taenia solium. The two-host life cycle of the tapeworm involves humans as definitive hosts and swine as intermediate hosts. Pigs are the source of human taeniasis, an intestinal tapeworm infection acquired by eating undercooked pork contaminated with cysticerci. Cysticercosis, however, is acquired by ingesting taenia eggs shed in the feces of a human carrier of tapeworms and thus may occur in people who do not eat pork and have no contact with pigs. Cysticercosis may also develop in tapeworm carriers through autoinfection. Although cysticerci may localize throughout the body, most clinical manifestations result from their presence in the central nervous system, where they can cause seizures, hydrocephalus, and other neurologic problems.1
Cysticercosis is endemic in rural areas of Latin America, Asia, and Africa.1 2 3 4 The number of cases of neurocysticercosis diagnosed in the United States increased greatly during the 1980s because of the improved images of the brain offered by CT and magnetic resonance imaging scans1 , 5 and the increasing number of emigrants from areas in which cysticercosis is endemic.6The disease is diagnosed most frequently in California and other western states in immigrants who acquired their infections outside the United States. In the eastern United States neurocysticercosis is reported less frequently.7 , 8 Cases of the disease are not required by law to be reported to public health departments, however, and many cases may not come to the attention of public health authorities.
In June and July 1991, intracerebral infection with the larval form of the pork tapeworm T. soliumwas diagnosed in three unrelated persons with acute seizures. None of the patients had a history of recent foreign travel, and for religious reasons none ate pork. All were members of an Orthodox Jewish community in New York City. A preliminary inquiry revealed a fourth case, diagnosed in 1990, in a member of this community. We conducted an investigation to determine the sources of the infections, to ascertain whether family members of the index patients had also been infected, and to implement appropriate preventive measures.

METHODS

We reviewed the patients' medical records and diagnostic findings. We interviewed the patients and in some cases their parents. Diagnostic specimens (serum and stools) were collected from the patients' families and other household members. Stool specimens were examined for helminth eggs by routine concentration with ethyl acetate.9 Serum antibodies to cysticerci were measured by the enzyme-linked immunoelectrotransfer blot (EITB) assay performed at the Centers for Disease Control10 or, for the first case diagnosed, by an enzyme-linked immunosorbent assay (ELISA) performed at a commercial laboratory. To determine the frequency with which families in the community employed household helpers from outside the community, in December 1991 we performed a telephone survey of 71 families randomly selected from the membership list of the local community center.

RESULTS

Clinical Characteristics

The four patients, two female and two male, were 6 to 39 years of age when symptoms developed (Table 1TABLE 1Clinical and Serologic Characteristics of Four Patients in New York City with Neurocysticercosis and the Results of Serologic Screening of Immediate Family Members.). The illnesses were characterized by the onset of seizures in all four, heralded by aphasia in one. All patients were initially brought to hospital emergency rooms and admitted for a diagnostic evaluation and treatment. In all four patients, CT scanning and in some cases magnetic resonance imaging of the brain showed one (Patient 2) or two (Patients 1, 3, and 4) intraparenchymal ring-enhanced lesions measuring 7 mm to 2 cm in diameter. A CT scan of the brain in Patient 3 revealed scattered punctate calcifications in addition to the two ring-enhanced lesions. Plain-film radiographs of Patient 3 demonstrated two ellipsoid calcifications (measuring 3 by 8 mm) in each thigh. All patients were evaluated extensively for tumors, infections, and other potential causes of the brain lesions. Serologic tests for cysticercosis were performed for all patients: the EITB assay was positive in three patients, and the ELISA was negative in the fourth (Patient 1). Serum was not available from Patient 1 to retest with the EITB assay. A brain biopsy was performed in Patients 1 and 4; tissue samples removed from both patients were identified as larval cestodes of the cysticercal type (T. solium). Patients 1 and 3 were treated with praziquantel (50 mg per kilogram of body weight per day for 15 days, given with corticosteroids). At the time of the most recent follow-up visit, three patients who were taking anticonvulsants remained seizure-free. Patient 1 stopped taking anticonvulsant medication after six months, with no recurrence of seizures. Patient 4 has residual weakness of his right foot.

Epidemiologic Findings

Patients 1 and 4 were born in New York City, and Patient 3 was born in New Jersey. Patient 2 was born in Morocco but has lived in the United States since 1976. Only Patient 4 had traveled to an area in which cysticercosis was known to be endemic; his trip lasted one week and was completed eight years before he became ill. All the patients were Orthodox Jews, and they and other family members adhered to the religious dietary proscription against eating pork. All stool examinations during the initial diagnostic evaluations were negative for tapeworm or other helminth eggs.
Members of the patients' immediate families were screened serologically for evidence of exposure to cysticercosis, and seven relatives of Patients 2 and 4 had positive EITB tests (Table 1). All 11 family members, whether seropositive or seronegative, were examined further for neurocysticercosis by magnetic resonance imaging of the brain. Lesions were found in two seropositive children of Patient 2. Her six-year-old daughter had a cystic lesion in the right occipitoparietal region, and her two-year-old daughter had a single cystic lesion surrounded by edema in the left occipitoparietal region. Five other seropositive and four seronegative relatives of Patients 2 and 4 had normal results on magnetic resonance imaging. All the family members had previously been well; however, the six-year-old seropositive daughter had a prolonged seizure and was hospitalized one day before her scheduled magnetic resonance imaging scan. Both children with imaging abnormalities and positive serologic results were treated with praziquantel (50 mg per kilogram per day) for 15 days.
The families of the four index patients all employed housekeepers who had recently emigrated from Latin American countries where T. solium infection is endemic. Two housekeepers were living in the home of Patient 1 when she became ill. Serum specimens from one of the housekeepers, drawn in February 1990 and tested for cysticercus antibodies at a commercial laboratory, were positive (ELISA titer, 1:320), and an examination of stool specimens revealed eggs of taenia species. This woman had lived with Patient 1 for the previous 10 years but had returned to her village in Oaxaca, Mexico, on vacation each year. When advised of the test results, both employees refused a further interview or treatment and left the home.
During the five years before Patient 2 became ill, the family had employed at least 10 women as housekeepers. Only one, a woman employed in the household since December 1990, was tested. Stool examinations for taenia eggs and serum assays for cysticercus antibodies were negative.
The family of Patient 3 had employed several women of Latin American origin during the child's lifetime. Stool and serum specimens obtained in October 1991 from a housekeeper who had been with the family for 2 1/2 years were negative.
For six years before Patient 4 became ill, the family had continuously employed Hispanic women as housekeepers, but at the time of our investigation in October 1991 none were living in the household. Since Patients 2 and 4 and their families frequently socialized together and shared meals, our attention was drawn to two women who had been employed by these families in the summer of 1990, when both families vacationed together. Stool and serum specimens from the woman who had been employed by Patient 4 were negative for taenia eggs and cysticercus antibodies, respectively. The woman who had worked for Patient 2 in the summer of 1990 had returned to her village in Puebla, Mexico. She was located there by Mexican health authorities in March 1992 and agreed to submit stool and serum specimens from herself and family members. Stool specimens from this 29-year-old woman, her husband, and five children, who were 6 to 10 years of age, were negative for taenia eggs. However, the woman and her eight-year-old daughter both had positive EITB tests. The woman had always lived in the same rural village in Mexico, except for the period from January to August 1990 when she had lived in New York City and worked for Patient 2. Although her cousin from the same village reportedly had been given a diagnosis of neurocysticercosis, neither the woman nor members of her immediate family had a medical history suggestive of neurocysticercosis.
The community in New York City where all the patients live is composed of approximately 35,000 people belonging to 6000 to 8000 families. Results of the telephone survey showed that 94 percent of the families employed housekeepers. All the employees were women, and 89 percent had emigrated from Mexico or other Latin American countries in which T. solium infection is endemic. Each family had employed an average of more than three such women in the previous five years.

DISCUSSION

The four patients we describe together with the seven seropositive family members represent a unique geographic and temporal cluster of locally transmitted neurocysticercosis. Travel histories of the patients were not consistent with exposure to the infection in countries in which T. soliuminfection is endemic. All the patients and their families adhered to Orthodox Jewish dietary laws, which forbid the eating of pork. Moreover, T. solium taeniasis due to the ingestion of contaminated pork is extremely unlikely in the United States. Cysticerci were detected in only 3 of more than 83 million hogs examined after slaughter under federal inspection in 1990.11
A review of more than 900 cases of cysticercosis in the United States indicates that more than 90 percent of affected patients were born outside this country, the great majority (80 to 90 percent) in Mexico.12 13 14 15 16 17 18 19 20 21 22 23 Through 1986, only 15 cases of locally acquired disease had been reported in the United States.20 From 1988 through 1990, 10 of the 138 cases reported to the Los Angeles Department of Health Services were acquired locally.24 Epidemiologic investigations of locally acquired cases have occasionally identified persons who had acquired tapeworm infections outside the United States as probable sources of infection.7 , 15 , 17 , 24
The most likely sources of infection in the patients described in this report were women living and working in the patients' homes who had recently emigrated from Latin American countries where T. solium infection is endemic. The demonstration of active infection with taenia species in a housekeeper who worked for the family of Patient 1 and the positive serologic findings in a housekeeper formerly employed by Patient 2 support this hypothesis. It was not possible to identify the species of taenia responsible for the housekeeper's infection because no proglottids were recovered and the eggs of T. solium and T. saginata are indistinguishable; both species are prevalent in Mexico. However, the fact that antibodies were detected in the serum of both housekeepers is indicative of exposure to T. solium, since persons with T. saginata taeniasis do not have antibodies detectable with the EITB assay,25 whereas carriers of T. solium often do.26
The identification of the sources of these infections was hindered by the frequent turnover of housekeepers in the households and our inability to contact former employees. For example, in the five years before Patients 2 and 4 became ill, more than 20 women had worked in their homes. Another factor was the difficulty of determining when transmission occurred: the period between the acquisition of infection and the onset of neurocysticercosis ranges from a few months to more than 10 years.1 , 20 The identification of a seropositive two-year-old child in the household of Patient 2 implies that the transmission of the disease had occurred fairly recently. Finally, conventional stool examinations are not a highly sensitive method of detecting infections with taenia species because eggs are released in feces irregularly.27
Because persons infected with T. solium tapeworms intermittently shed proglottids and substantial numbers of infective eggs in their stools, others can be exposed to cysticercosis by the fecal—oral route. People become infected by transferring the eggs from their hands to their mouths after direct contact with a tapeworm carrier or by ingesting contaminated food, water, soil, or fomites. Taenia eggs, which are infective as soon as they are excreted from the host, have been recovered from the dirt under the fingernails of tapeworm carriers as well as from their skin and clothes.27 , 28 The risk that eggs will be transferred to others is increased when such persons prepare and serve food. Thus, at least some of our cases are likely to have been foodborne. On the basis of the pattern of social contact among the patients' families, we believe that at least three tapeworm carriers were responsible for the infection of the four patients and the seropositivity of seven family members. The same tapeworm carrier may have infected Patients 2 and 4 and their seropositive relatives because these families frequently socialized and ate together.
The nature and severity of the signs and symptoms of neurocysticercosis are quite variable and depend on the numbers and location of cysticerci and the severity of the host's inflammatory response.1 Seizures are the most frequently reported finding in cases in the United States,12 13 1415 16 17 18 19 20 21 22 and they were the clinical events that brought all the cases reported here to medical attention. Praziquantel, which was given to the patients with viable cysts, is a highly effective treatment for patients with intraparenchymal cysts.1
In Patients 1 and 2, the interval between the onset of illness and the diagnosis of neurocysticercosis was four to seven months despite the use of modern diagnostic imaging procedures. Apparently there was no consideration of neurocysticercosis in the initial diagnostic workup because the patients had no history of residence or extensive travel in countries in which T. solium infection is endemic. Either the patients' association with household employees who had recently emigrated from areas in which cysticercosis is endemic was not elicited, or the importance of such an association was not appreciated. Only in the case of Patient 3 were the radiologic findings immediately interpreted as suggestive of neurocysticercosis; the diagnosis was then confirmed by the EITB assay. The timely use of this highly sensitive and specific assay can obviate the need for an invasive biopsy for diagnosis.10 , 29 , 30
There is a potential for the continued transmission of the infection. A large proportion of the 6000 to 8000 families in this community employ housekeepers who have recently emigrated from Latin American countries, where the estimated prevalence of T. solium taeniasis is 1 to 5 percent.7 , 25 ,31 32 33 We estimated that between 50 and 300 additional families in the community may have a tapeworm carrier working in their homes.
Patients with cysticercosis and members of their immediate family and households should be screened for tapeworm infection. Treatment with a single dose of niclosamide or praziquantel can eradicate the tapeworm34 and remove a potential source of transmission. Persons at high risk for T. solium infections should be screened for intestinal parasites if they seek work as housekeepers or food handlers.
We are indebted to Dr. Mary Guinan, Dr. Dennis Juranek, and Ms. Phyllis Moir of the Centers for Disease Control and to Dr. Kenneth R. Ong and Ms. Eleanor Bell of the New York City Department of Health for useful advice; to Mr. Michael G. Witkes and Ms. Nitza Hannan for obtaining information from members of the New York City community affected by the disease; to Ms. Susanna Gonzalez (Directorate of Epidemiology, Federal Ministry of Health, Mexico City) for obtaining specimens and information from the contact traced to Mexico; and to Dr. Agustin Plancarte, Mr. Ricardo Sarti, and Ms. Silvia Valencia (Biomedical Institute, Mexico City) for performing laboratory studies in Mexico.

SOURCE INFORMATION

From the Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control, Atlanta (P.M.S., A.C.M., M.W.); the Department of Pediatrics, New York University Medical Center, New York (J.L.M., D.P.); the Infectious Diseases Division (B.J.H.) and Department of Neurology (J.A.S.), Cornell University School of Medicine, New York; the Division of Pediatric Neurology, Mount Sinai Hospital, New York (A.M.A.); the General Directorate of Epidemiology, Secretariat of Health, Mexico City, Mexico (E.S.); and the Biomedical Research Institute, Mexico City, Mexico (A.F.). Address reprint requests to Dr. Schantz at the Division of Parasitic Diseases (F13), Centers for Disease Control, Atlanta, GA 30333.

Sunday, August 13, 2017

Parsifal Sydney


Parsifal powerful but could use more of the rite stuff


Conductor Pinchas Steinberg, left, with tenor Jonas Kaufmann as Parsifal. Picture: Keith Saunders
Conductor Pinchas Steinberg, left, with tenor Jonas Kaufmann as Parsifal. Picture: Keith Saunders
Parsifal was Richard Wagner’s operatic swan song. In its renunciation of worldly pleasures and desires in favour of redemption and transcendent grace, it encapsulated the composer’s intellectual and spiritual journey.
It also is the most problematic of Wagner’s operas to present in concert. By eschewing any visual or design element apart from lighting, this Opera Australia performance unwittingly diluted the opera’s impact.
The religious ceremonies in the first and third acts, for instance, are accompanied solely by long stretches of orchestral music. Despite being exquisitely played by the Opera Australia Orchestra, one had little sense of their ritual power. Ultimately, one was left marvelling at the genius of the music but slightly unmoved by the drama.
Wagner had strong views about how tempos should be employed in his operas. Fortunately, conductor Pinchas Steinberg unerringly chose the right tempos. His measured pacing enabled the composer’s expansive, long-breathed lines to soar. Maintaining good balances and clear textures, his subtly applied doses of accelerando and smoothly shaped crescendos generated momentum and excitement when needed.
German tenor Jonas Kaufmann was acclaimed for his performances as Parsifal at the Metropolitan Opera in New York in 2013. His interpretation here was just as fine. Through voice and gesture alone, Kaufmann charted the protagonist’s spiritual journey. All wide-eyed, clear-voiced innocence in Act I, his exquisite soft-grained sotto voce passages captured his character’s sense of wonder and ultimate serenity while his forceful clarity and ringing top register power realised Parsifal’s moments of anguished uncertainty.
Although Kaufmann was the star drawcard, his castmates were equally outstanding. American mezzosoprano Michelle DeYoung made a spectacular impact as Kundry. Strong across her range, her sinuous phrasing, strong dynamic control and appealing tone colours conveyed Kundry’s dual role as siren and penitent. Displaying remarkable stamina and superb diction, Korean bass Kwangchul Youn (Gurnemanz) sang with stentorian power and a focused sense of line, embodying his noble character’s moral authority.
Firm-voiced baritone Michael Honeyman gave an expressive performance as the guilt-racked Amfortas. By contrast, the hard-edged timbre of fellow baritone Warwick Fyfe created a gripping portrayal as the evil sorcerer Klingsor. Bass David Parkin was an imposing Titurel while six of Opera Australia’s leading sopranos and mezzos made an alluring bevy of flower maidens.

Parsifal review: Opera Australia's performance as close to ideal as possible



Parsifal, by Wagner
Opera Australia. Opera House Concert Hall. August 9

★★★★★*
In assembling a cast as close to ideal as one could decently expect, a conductor of venerable wisdom and experience in Pinchas Steinberg, and setting free the sound of a usually straitjacketed orchestra and chorus to weave and waft around the Concert Hall's ample acoustic accommodation, Opera Australia' concert performance of Wagner's most sonically sophisticated opera, Parsifal, creates for listeners a direct path to its essence.
That essence is pure spirit expressed in sound, both sullied and cleansed, both in anguish and in bliss.
Music has always gravitated towards the spirit – it is its natural domain. By stripping away the myriad plot details of Wolfram von Eschenbach's 13th century poem to leave a simple symmetrical three-act structure pivoting around a moment of self-realisation and transformation, Wagner not only crowned his own not-insubstantial achievements, but also created one of the greatest works in the repertoire.
It helps, of course, to have one of the world's great Parsifal singers, Jonas Kaufmann, in the title role. Kaufmann's approach is one of noble restraint.
There is never a hint of flamboyance or contrivance; the whole expressive weight is carried by the voice quality and immaculate polish of tone; by careful modulation of dynamic, colour and intensity; and by purity of diction and vowel.
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In the first act and a half, when the character of Parsifal is protected from corruption by unknowing foolishness, Kaufmann was subdued and dissembling like a youth who had smashed the family car and wanted to be somewhere else.
He opened out with magnificently polished focus after the transformative kiss at the centre of Act 2, each phrase beautifully sculpted and graded, each crucial moment spellbinding.
Michelle DeYoung as Kundry also broadens in this crucial transformation. In the first act her voice was richly portentous and coloured. In the seduction of Act 2, she added enveloping warmth and forceful power.
It is key to the work that this duet be the fulcrum, and here it became a riveting point of central focus.
As the wise Gurnemanz, Kwangchul Youn sang with mahogany depth and wonderfully textured roundedness, sustaining this character's crucial framing reflections in the outer acts with centred dignity.
Taking the role of the wounded Amfortas, who represents the spirit in agony, Michael Honeyman's voice captured rich autumnal colours to bring out the character's poignancy.
The image Wagner created of the open bleeding wound to represent a self-inflicted fall from grace, brings to mind the art of Francis Bacon.
That image is taken further in the figure of the self-castrated Klingsor, to whose impotent malevolence Warwick Fyfe brought terrifying ferocity, a keen-edged incisive voice, madly wandering eye and brilliant character portrayal.
David Parkin was stern and sepulchral as the ageing Titurel. Under Steinberg, the great glory of the Opera Australia Orchestra and Chorus was the subtle balance of tone and floating sense of pulse, creating finely graded textures, some firmly grounded and richly blended, others rising above the bass like delicately fractured clerestory light.
Descriptions of Wagner's conducting stress his complete freedom, but Steinberg achieved the unbounded effect of chant and dreamlike association through inner discipline and carefully weighed balance.
Musically, this is one of Opera Australia's outstanding performances in recent decades, leaving the theatrical element to blossom in the imagination.
*While the Herald only rates performances out of five, Peter would have awarded Parsifal 5½ stars if permitted.
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Here is what he has told the Paris Opera:

I’m sorry that my cancellations have been the source of a lot of disappointment and frustration over the past few weeks.

Of course, I can understand the irritation of all those who had organized the expensive trips to come and listen to me. Unfortunately, the performance of a voice of singer cannot be guaranteed and sometimes a singer is facing events that require it to take a long rest.

When I noticed that something was wrong with my voice, at first I thought it was a beginning of infection. The medical examination, however, has given a different result: the side effects of a medicine made burst a small vein on my vocal cords.

So I must stop singing until the haematoma has completely subsided. To avoid permanent damage. Thus, it is with a heavy heart that I must also cancel my representations of the Tales of Hoffmann in Paris.
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Friday, July 14, 2017

Diet & Statin

Dr Mark Porter: The diet that’s almost as good as statins — and I’m proof that it works
Dr Mark Porter

Published at 12:01AM, February 16 2016


Older folk can expect a longer retirement, according to a new report from Public Health England, which shows that over-65s can look forward to another 20 years on average. Yet to enjoy those extra decades you will need an adequate pension and good health. I can’t help with the former but I do have a useful tip to maintain the latter.

At the beginning of the year I embarked on a six-week trial to see whether cutting back on carbohydrates could improve my poor cholesterol profile. The results are in and I am bowled over. The finer details are in the box below, but these are the headline results: I shed half a stone in weight, my cholesterol level dropped by 20 per cent, my triglyceride level by 30 per cent and, according to the risk calculator favoured by the NHS, my odds of succumbing to an early heart attack or stroke have dropped by nearly 15 per cent. Not quite the benefit you might expect from taking a statin, but as near as dammit.

Now I am well aware that one swallow doesn’t make a summer, and just because cutting back on carbs has had such a significant effect on my blood chemistry, it doesn’t mean it will work as well for you. Yet if you are one of the five million or so middle-aged people like me who, thanks to a combination of poor family history and high cholesterol levels, are eligible for statins, I would urge you to take a close look at your diet first. So what changes did I make, and where have the benefits come from?

First some context. At 6ft 2in and 14 stone, I wasn’t particularly overweight but I had a touch of middle-age spread with a BMI of 26 (25 is the upper limit of healthy). My cholesterol was raised (anywhere between 7.3 and 8 over recent years) and, although I ate a healthy diet, I have a sweet tooth and consumed far too much bread.

The plan was simple. I cut out all fruit juices, bread, cakes, biscuits and confectionery. And I restricted other starchy foods such as rice, pasta and potatoes. I carried on taking one sugar in my coffee and I had a free day on Sundays which, on at least one occasion, included sticky toffee pudding at my local pub. I made no other changes to my diet or lifestyle and the result would qualify at the upper end of what most people would regard as a low-carb diet, but it represented a significant reduction for me.

The resulting improvement in my blood profile could have come about in a number of ways. First, the weight loss will have helped. The drop in triglycerides (high levels of which are a risk factor for heart disease) is a direct result of fewer carbs, but a big reduction in fats may also have helped; I have eaten hardly any butter in the past six weeks. Not only is butter a keen component of my favoured sandwiches and rolls, it also features in many carb-rich foods such as cakes and other treats.

One other unintentional change was that I ended up eating more meat, eggs and cheese. Yet, while you would have expected this to have raised my cholesterol level, the opposite happened. And the latest research reflects this — while eating butter is bad for your cholesterol profile, eggs, cheese and lean meats don’t seem to have much impact.

Until I started this trial I was considering statins — which I have tried in the past — but my cardiovascular risk (qrisk.org) has dropped below the new 10 per cent threshold, so I am not going to worry for now.

My only regret is that I wish I had tried this in my twenties. I have never subscribed to the view that sugar is public enemy no 1 — there is so much more to disease than obesity and one nutrient — but I am a convert to the view that too much sugar and other carbs (which the body converts to sugar) are not good for us. My local bakery and my favoured sandwich shop may regret my decision but it is low carbs for me from now on.

The results at a glance

After six weeks cutting back on carbs my weight fell from 14st to 13st 7lb

My fasting cholesterol level fell from 7.3 to 5.9 and my triglycerides from 2.5 to 1.5

My “good” cholesterol (HDL) fell slightly from 1.3 to 1.2

I did not monitor my blood sugar levels because these have always been well into the healthy range, but those at risk of diabetes should expect a significant drop here too.