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Environmental Factors in Tiny Tim's Near-Fatal Illness
Abstract
Physicians, Dickens scholars, and historians have tried to diagnose the condition that affected Tiny Tim in A Christmas Carol. Leading entities include tuberculosis (TB), rickets, malnutrition, cerebral palsy, spinal dysraphism, and renal tubular acidosis. This article posits that an examination of the environment of London of 1820 to 1843 (when the novella was written) can provide important clues as to his condition. The blackened skies from burning coal, the crowding of people in tenements, the limited diet of the underclass, and the filth of London resulted in a haven for infectious diseases and rickets in children. Sixty percent of children in London had rickets, and nearly 50% had signs of TB. Tiny Tim likely had a combination of both diseases. After Ebenezer Scrooge's transformation, Scrooge could have ensured an improved diet, sunshine exposure, and possibly cod liver oil for Tiny Tim, which could have led to a "cure." Dickens was familiar with both rickets and TB and wrote about cod liver oil as a possible cure for rickets and scrofula. Improved vitamin D status can result in enhanced macrophage synthesis of 1,25-dihydroxyvitamin D, which increases the synthesis of the antimicrobial peptide cathelicidin (LL-37). This component of the innate immune system has strong killing properties for Mycobacterium tuberculosis. The combination of rickets and TB represent a crippling condition that could be reversed by improved vitamin D status.
... It goes without saying that disability studies on A Christmas Carol center around the character of Tiny Tim and his role in the narrative. Russel W. Chesney (2012), for instance, calls Tiny Tim Dickens's most famous medically based character and sets out to determine the causes of his mobility impairment, citing tuberculosis, polio, and renal tubular acidosis as probable reasons. Furthermore, he tries to depict how social factors like poverty and malnutrition may have exacerbated Tim's fragile health. ...
Disability was a ubiquitous image in the fiction of the nineteenth century, an age which witnessed controversial discussions regarding the questions of normalcy and deviance. Considered by many as the most famous writer of the period, Charles Dickens also widely employed disabled characters in his novels. One of the most memorable of these characters is Tiny Tim, a disabled child in Dickens's novella A Christmas Carol, whose pathetic condition greatly moves Scrooge, the narrative's notorious protagonist, facilitating and expediting his spiritual transformation. This paper aims to analyze the character of Tiny Tim and his influence on the main character in the light of the theory of narrative prosthesis. Introduced by disability critics David T. Mitchell and Sharon L. Snyder, the theory holds that disabled characters have served as prosthetic devices in many narratives; that is, they have not been appreciated, described, and understood for who they are as physically / mentally different people. Rather, they have only functioned as metaphors and symbols that have been constructed to convey a moral message to "normal" characters and readers. Research findings show that Tiny Tim exemplifies narrative prosthesis as his short presence in the work only reinforces the ableist discourse of the novella.
... Sin embargo, la presumible causa de su enfermedad ha sido fuente de permanente debate entre historiadores y médicos. 4, 5, 6 Dickens, un agudo observador de su entorno, jugó un papel relevante en la medicina al mostrar un variopinto grupo de afecciones 7 . ...
... However, the treatable elements to the description make tuberculosis (TB), vitamin D deficient rickets or renal tubular acidosis (RTA) possibilities. 31,32 Various remedies were available in Victorian London, more active sunlight exposure (vitamin D for rickets and TB), cod liver oil (vitamin D) or alkaline tonics (RTA) so that it is possible that the money given by Scrooge for Tim's medical care resulted in his life being saved. 32 Peter Pan (JM Barrie, 1911) Peter Pan is a boy who never grows up and has adventures in a magical world with his partner Wendy. ...
Our culture has a rich history of fairy tales, folklore and literature. These have all served a purpose, often to entertain, but also to moralise. Authors have often included interesting characters with identifiable medical conditions or described interesting characters that lend their names to conditions we can identify today. This paper looks at the medical conditions found in fairy tales, folklore and literature.
... Problematisch ist allerdings das Schicksal des kleinen "Tiny Tim", des jüngsten Sohnes. Er leidet unter einer nicht genau beschriebenen, möglicherweise tödlichen Krankheit, über die in pädiatrischen Fachzeitschriften kontrovers diskutiert wird, am wahrscheinlichsten handelt es sich um eine Kombination aus Rachitis und Tuberkulose(Chesney, 2012). Dass diesen sympathischen Jungen eine solche Krank-heit ereilt, macht Scrooge klar, dass ein "Gerechter Welt"-Glaube(Lerner, 1980) irrational ist. ...
Charles Dickens Weihnachtsgeschichte „Der Weihnachtsabend“ erzählt von der Wandlung des unbarmherzigen, gefühlskalten Geschäftsmannes Ebenezer Scrooge in einen mitfühlenden, warmherzigen Menschen. Seit ihrer Veröffentlichung im Jahr 1843 rührt sie Millionen von Menschen. Sieht man die Geschichte als einen therapeutischen Fallbericht an, passiert hier Ungeheuerliches: Eine Persönlichkeitsänderung um 180 Grad – in einer Nacht!
Eine hoch effektive Kurzzeittherapie. Und das bei katastrophaler motivationaler Ausgangslage und rigiden Schemata. Dickens Geschichte lässt sich nicht nur als Fundgrube für therapeutische
Methoden verwenden, vielmehr bietet sie das Rahmenmodell einer Integrativen Therapie von Sinnproblemen.
Aim:
To review potential benefits of vitamin D supplementation in critically ill patients.
Methods:
The data were collected by searching Scopus, PubMed/Medline, ScienceDirect, Clinical trials and Cochrane database systematic reviews. The keywords used as search terms were 'vitamin D', 'critically ill patients', 'ICU' and 'sepsis'.
Results & conclusion:
Vitamin D deficiency is common in patients admitted to emergency departments, medical and surgical intensive care units. Positive effects of vitamin D on the immune system through decreasing inflammatory cytokines and increasing natural anti-infective molecules have been reported. Patients with low serum vitamin D concentrations experienced longer hospital stay and were more prone to nosocomial infections, including blood stream and respiratory infections. However, a correlation between vitamin D serum level and patients' mortality is not fully described. Limited studies have assessed effects of vitamin D supplementation on morbidity and mortality in critically ill patients. In the future, well-designed randomized clinical trials should describe the best dose, route and duration of vitamin D supplementation in critically ill patients.
In 1889 Dr. John Bland-Sutton, a prominent London surgeon, was consulted about fatal rickets in over 20 successive litters of lion cubs born at the London Zoo. He evaluated the diet and found the cause of rickets to be nutritional in origin. He recommended that goat meat with crushed bones and cod-liver oil be added to the lean horsemeat diet of the cubs and their mothers. Rickets were reversed, the cubs survived, and subsequent litters thrived. Thirty years later, in classic controlled studies conducted in puppies and young rats, the definitive role of calcium, phosphate and vitamin D in prevention and therapy of rickets was elucidated. Further studies led to identifying the structural features of vitamin D.
Although the Bland-Sutton diet provided calcium and phosphate from bones and vitamins A and D from cod-liver oil, some other benefits of this diet were not recognized. Taurine-conjugated bile salts, necessary for intestinal absorption of fat-soluble vitamins, were provided in the oil cold-pressed from cod liver. Unlike canine and rodent species, felines are unable to synthesize taurine, yet conjugate bile acids exclusively with taurine; hence, it must be provided in the diet. The now famous Bland-Sutton “experiment of nature,” fatal rickets in lion cubs, was cured by addition of minerals and vitamin D. Taurine-conjugated bile salts undoubtedly permitted absorption of vitamins A and D, thus preventing the occurrence of metabolic bone disease and rickets.
This case control study was conducted to determine the frequency of nutritional rickets among hospitalized infants and to assess their relation to respiratory diseases. All infants between the age of 3 months and 2 years admitted to the pediatric ward of Queen Alia Military Hospital during the period February-October 2001 were examined and investigated to rule out nutritional rickets. Children admitted for the first time to hospital for acute illnesses were only included in the study. A special data collection sheet was designed for this study which includes information on the age, sex, causes of admission, family size, the rank of the child in the family, family monthly income, outdoor clothing habit of the mother, and the mode of feeding. Data were collected from the infant charts and/or by interviewing the child's mother or guardian. Clinical signs of rickets were also recorded, including rosary beads, craniotabes, wide anterior fontanel, delayed dentition, widening of epiphysis, bowing of the legs, and double malulous. Blood sample was collected for calcium, phosphorus, alkaline phosphatase, and hemoglobin level. Those infants with any clinical sign of rickets and/or abnormal chemical results had a wrist X-ray to confirm the diagnosis of rickets. The rachitic group (cases) was compared for statistical significance with the remaining non-rachitic infants (controls) for the data collected. Rachitic infants received intramuscular 600,000 IU of vitamin D; a follow-up wrist X-ray and blood sample for calcium, phosphorus and alkaline phosphatase was arranged 3 weeks later. Forty-seven infants (10.6 per cent) out of the 443 included in the study were found to have nutritional rickets. Forty (85.1 per cent) of the rachitic infants were admitted due to lower respiratory tract diseases compared with 30 per cent of the control group and the difference was statistically significant (p < 0.01). Duration of hospital stay in the rachitic infants was also significantly more prolonged than the non-rachitic control group (9.5 days vs. 7.4 days, p = 0.002). Rachitic infants were breastfed in 82.9 per cent, ranked second or more in the family in 87.2 per cent, and had mothers who wore head cover outdoors in 80.8 per cent compared with 60.8, 40.1, and 60.3 per cent, respectively, in the non-rachitic group (p < 0.01). High alkaline phosphatase, hypocalcemia, hypophosphatemia, and anemia was found in 100, 19, 50, and 78.7 per cent, respectively, in the rachitic group compared with 9.8, 2, 1.2, and 43.7 per cent, respectively, in the control group (p < 0.001). Nutritional rickets seems to be a common problem among infants in Jordan. Further studies at national level are needed to determine the prevalence of rickets in Jordan. Rachitic infants are commonly hospitalized due to lower respiratory tract infections, thus there is a high index of suspicion for rickets among hospitalized infants with lower respiratory tract diseases.
Persistent Mycobacterium tuberculosis (MTB) likely encounters a phosphate-limited environment within macrophage phagosomes. We studied MTB growth, antibiotic susceptibility,
and gene expression during phosphate limitation. With use of MTB mutants deficient in phosphate-related genes, we assessed
bacillary survival under phosphate-limited conditions and in mouse and guinea pig lungs. Phosphate limitation restricted MTB
growth in a dose-dependent manner, and phosphate-starved bacilli became phenotypically tolerant to isoniazid. The MTB genes
ppk1 and relA were upregulated significantly after phosphate starvation, consistent with inorganic polyphosphate accumulation and MTB stringent
response induction. The phosphate-specific transport operon pstS3-pstC2-pstA1 was induced during phosphate starvation and its expression was dependent on the 2-component regulatory system SenX3-RegX3.
The MTB gene regX3 appears to be essential for bacillary survival during phosphate limitation and in mammalian lungs. Our data suggest that
MTB encounters phosphate-limited conditions during mammalian lung infection and that expression of the phosphate starvation
response (PSR) is important for MTB persistence
The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D) enhances innate immunity by inducing the cathelicidin antimicrobial peptide (hCAP). In monocytes/macrophages, this occurs primarily in response to activation of TLR, that induce expression of the vitamin D receptor and localized synthesis of 1,25(OH)(2)D from precursor 25-hydroxyvitamin D(3) (25OHD). To clarify the relationship between vitamin D and innate immunity, we assessed changes in hCAP expression in vivo and ex vivo in human subjects attending a bone clinic (n = 50). Of these, 38% were vitamin D-insufficient (<75 nM 25OHD) and received supplementation with vitamin D (50,000 IU vitamin D(2) twice weekly for 5 wk). Baseline 25OHD status or vitamin D supplementation had no effect on circulating levels of hCAP. Therefore, ex vivo changes in hCAP for each subject were assessed using peripheral blood monocytes cultured with 10% autologous serum (n = 28). Under these vitamin D "insufficient" conditions the TLR2/1 ligand 19 kDa lipopeptide or the TLR4 ligand LPS, monocytes showed increased expression of the vitamin D-activating enzyme CYP27b1 (5- and 5.5-fold, respectively, both p < 0.01) but decreased expression of hCAP mRNA (10-fold and 30-fold, both p < 0.001). Following treatment with 19 kDa, expression of hCAP: 1) correlated with 25OHD levels in serum culture supplements (R = 0.649, p < 0.001); 2) was significantly enhanced by exogenous 25OHD (5 nM); and 3) was significantly enhanced with serum from vivo vitamin D-supplemented patients. These data suggest that a key role of vitamin D in innate immunity is to maintain localized production of antibacterial hCAP following TLR activation of monocytes.
The vitamin D endocrine system is essential for calcium and bone homeostasis. The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxyvitamin D [1,25-(OH)2D], can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). Absence of a functional VDR or the key activating enzyme, 25-OHD-1α-hydroxylase (CYP27B1), in mice creates a bone and growth plate phenotype that mimics humans with the same congenital disease or severe vitamin D deficiency. The intestine is the key target for the VDR because high calcium intake, or selective VDR rescue in the intestine, restores a normal bone and growth plate phenotype.
The VDR is nearly ubiquitously expressed, and almost all cells respond to 1,25-(OH)2D exposure; about 3% of the mouse or human genome is regulated, directly and/or indirectly, by the vitamin D endocrine system, suggesting a more widespread function. VDR-deficient mice, but not vitamin D- or 1α-hydroxylase-deficient mice, and man develop total alopecia, indicating that the function of the VDR and its ligand is not fully overlapping. The immune system of VDR- or vitamin D-deficient mice is grossly normal but shows increased sensitivity to autoimmune diseases such as inflammatory bowel disease or type 1 diabetes after exposure to predisposing factors. VDR-deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status.
The innate immune response in human tuberculosis is not completely understood. To improve our knowledge regarding the role
of cathelicidin hCAP-18/LL37 in the innate immune response to tuberculosis infection, we used immunohistochemistry, immunoelectron
microscopy, and gene expression to study the induction and production of the antimicrobial peptide in A549 epithelial cells,
alveolar macrophages (AM), neutrophils, and monocyte-derived macrophages (MDM) after infection with Mycobacterium tuberculosis. We demonstrated that mycobacterial infection induced the expression and production of LL-37 in all cells studied, with AM
being the most efficient. We did not detect peptide expression in tuberculous granulomas, suggesting that LL-37 participates
only during early infection. Through the study of Toll-like receptors (TLR) in MDM, we showed that LL-37 can be induced by
stimulation through TLR-2, TLR-4, and TLR-9. This last TLR was strongly stimulated by M. tuberculosis DNA. We concluded that LL-37 may have an important role in the innate immune response against M. tuberculosis.
How important was coal to the Industrial Revolution? Despite the huge growth of output, and the grip of coal and steam on
the popular image of the Industrial Revolution, recent cliometric accounts have assumed coalmining mattered little to the
Industrial Revolution. In contrast both E. A. Wrigley and Kenneth Pomeranz have made coal central to the story. This article
constructs new series on coal rents, the price of coal at pithead and at market, and the price of firewood, and uses them
to examine this issue. We conclude coal output expanded in the Industrial Revolution mainly as a result of increased demand
rather than technological innovations in mining. But that expansion could have occurred at any time before 1760. Further,
our coal rents series suggests that English possession of coal reserves made a negligible contribution to Industrial Revolution
incomes.
The soaring prices of oat across the German state of Baden prompted the invention of the first bycicle, velocipede, by Karl Drais, Germany, in 1817, as a replacement for the horse. The velocipede had no pedals or cranks, so the riders had to scoot along by pushing with their foot. Drais's idea was to replace horse by human power, and his first machines were four-wheelers driven by a treadmill or cranks attached to the rear axle. Drais continued to be a creative inventor, with innovations including the first typewriter with a keyboard, a stenograph that could emboss 1000 letters a minute, and a more efficient wood stove and a haystack for slow cooking.
… the great expence [sic] of land carriage will ever deprive us of many useful and desirable articles, particularly mines and minerals, which must lie dormant in the bowels of the earth, to the great loss of the landowner and the public, unless some more cheap and expeditious way of carriage be opened to the internal parts of the country.†
… there can be no doubt that a greater extension of our distant navigation has arisen from a system which has, in effect, converted the internal parts of our island into coasts.‡
Vitamin D plays a major role in bone mineral density and calcium homeostasis. Apart from its classical action, the active form of vitamin D [1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))] influences the innate and adaptive immune functions through vitamin D receptor (VDR) that are present in various cells of the immune system. Vitamin D deficiencies have been associated with development of tuberculosis (TB) disease, caused by Mycobacterium tuberculosis. Vitamin D(3) is shown to enhance macrophage phagocytosis of M. tuberculosis and increases the production of antimicrobial peptide cathelicidin and killing of M. tuberculosis. During the preantibiotic era, exposure to sunlight and supplementation of vitamin D were the methods of choice for treatment of TB. Vitamin D supplementation showed sputum clearance and radiological improvement and reduction in mortality among human immunodeficiency virus (HIV)-infected patients with TB. VDR gene polymorphisms regulate the immunomodulatory effect of vitamin D(3) and are associated with faster sputum conversion during anti-TB treatment. The emerging evidences regarding immunomodulatory properties of vitamin D(3) have rekindled interest in vitamin D as an adjunct to anti-TB therapy. The current review explains the important potential application of vitamin D in enhancing the innate immunity to TB and the role of VDR gene variants on anti-TB treatment.
Over the past 20 y, a resurgence in vitamin D deficiency and nutritional rickets has been reported throughout the world, including the United States. Inadequate serum vitamin D concentrations have also been associated with complications from other health problems, including tuberculosis, cancer (prostate, breast, and colon), multiple sclerosis, and diabetes. These findings support the concept of vitamin D possessing important pleiotropic actions outside of calcium homeostasis and bone metabolism. In children, an association of nutritional rickets with respiratory compromise has long been recognized. Recent epidemiologic studies clearly demonstrate the link between vitamin D deficiency and the increased incidence of respiratory infections. Further research has also elucidated the contribution of vitamin D in the host defense response to infection. However, the mechanism(s) by which vitamin D levels contribute to pediatric infections and immune function has yet to be determined. This knowledge is particularly relevant and timely, because infants and children seem more susceptible to viral rather than bacterial infections in the face of vitamin D deficiency. The connection among vitamin D, infections, and immune function in the pediatric population indicates a possible role for vitamin D supplementation in potential interventions and adjuvant therapies.
Radiologically diagnosed rickets was found to be common in children of the poorer classes in Tehran. It was frequently associated with gastroenteritis or bronchopneumonia and a large proportion of the children were severely underweight for their age. In children below the age of 1 year malnutrition tended to mask the signs of rickets. Convulsions were much less frequent in the malnourished children; the concentration of calcium in the serum was higher and that of alkaline phosphatase was lower than in those who were well nourished. Biochemistry is of little value in the diagnosis of rickets in the presence of malnutrition.
• One of the most endearing characters in English literature is Tiny Tim, the crippled son of Ebenezer Scrooge's clerk, Bob Cratchit. Yet the nature of Tiny Tim's multifaceted and implicitly reversible illness is a mystery and open to debate and speculation. From details of the original manuscript and the eight film versions, it is possible to construct a differential diagnosis for Tim's short stature, asymmetric crippling disorder, and curious intermittent weakness that would lead to his death, if untreated, within a period of 1 year. Following the ghostly visitations, Scrooge vows to assist the struggling Cratchit family financially, thereby making available the best medical care money could buy. From review of pediatrics texts from 1830 to 1850, a recommended treatment plan would have included (1) general measures such as country air and exercise, and fish oils such as cod and halibut (vitamin D), and (2) specific treatments of tonics (containing combinations of belladonna, opium, sodium bicarbonate, sodium citrate, and potassium chloride) emphasizing alkalis, and splinting and bracing the limbs. Such treatments with vitamin D and alkalinization with sodium bicarbonate and sodium citrate suggest the plausible speculation that Tiny Tim had renal tubular acidosis (type I), a disorder that is characterized by growth failure and, if left untreated, complicated by osteomalacia with pathologic fractures, hypokalemic muscle weakness and periodic paralysis, nephrocalcinosis leading to renal failure, and death. I propose that Tiny Tim had distal renal tubular acidosis (type I).
(AJDC. 1992;146:1403-1407)
Sir.—Of all the haunting images that moved the hardened heart of Ebenezer Scrooge on that infamous Christmas Eve, the picture of Tiny Tim seemed to touch him most deeply. Tiny Tim, perhaps the most pathetic yet endearing character in Dickens' story, A Christmas Carol, suffered from a crippling condition. "Alas for Tiny Tim, he bore a little crutch and had his limbs supported by an iron frame." Sitting by the fire after Christmas dinner, Bob Cratchit held Tim's "... withered little hand in his, as if he loved the child, and wished to keep him by his side, and dreaded that he might be taken from him."
Dickens has little more to say about the boy's illness. Tim might have had any one of a number of congenital abnormalities of his limbs. In an age before corrective surgery and prosthesis, he was likely destined to remain a cripple for life.
Although the relationship between breathing and sleep has only recently been "discovered" by the medical community, excellent literary descriptions of what we know to be the sleep apnea syndrome were made long ago. Although ancient Greek writings described probable sleep apnea, the most important literary contributions in this area are by Charles Dickens. His description of Joe the fat boy in the Pickwick Papers is an example of his brilliant skills of observation and description. It was not until about 140 years after Pickwick Papers was published that we understood what he was describing.
In 10 patients with renal tubular acidosis, seven with type I and three with Fanconi syndrome, simultaneous measurements of vitamin D metabolites and electrolytes were made. No marked abnormalities of calcidiol2, calcidiol3, 24,25(OH)2D, or calcitriol were found in these patients, whose mean serum HCO3 was 18 +/- 3 mM/L (SD). Further, no relationship between serum HCO3 and calcitriol could be found. These results suggest that either vitamin D deficiency may be required before any alterations in the production of calcitriol are seen, or that the effects of acidosis in animals may not be reflected in humans. Further, it appears less likely that the bone disease found in renal tubular acidosis is related to abnormalities in vitamin D metabolism resulting from systemic acidosis, but that bone disease is more likely related to the acidosis and hypercalcuria prevalent in this disorder.
Sir.—It is fitting that Lewis proposes that Charles Dickens' Tiny Tim was afflicted with renal disease,1 since a number of Dickensian characters have autobiographical attributes. Charles Dickens was reported to suffer much of his life from renal colic and may have died of kidney failure.2 The fact that he had "strokes" at a relatively young age suggests he also may have had the attendant hypertension of chronic renal failure. In addition, John Dickens, Charles' father, suffered from a form of kidney disease since his death was related to the removal of a bladder stone.2
Lewis speculates that Tiny Tim could have had distal RTA type 1, citing Dickens' descriptions of Tim's symptoms and considering the potential treatability of such an illness in 19th-century England. Other writers have suggested that poor Tim may have suffered from polio, tuberculosis of the hip, or pseudocoxalgia.3 While it is
Sir.—I read with interest the article by Lewis1 in the December 1992 issue of AJDC. This fascinating article suggests that Tiny Tim had RTA type 1 to account for his crippling disorder so dramatically presented in eight film versions, illustrated books, and hundreds of stage presentations. This is an intriguing possibility because it represents a potentially reversible form of childhood rickets. Nevertheless, I believe that there are a number of points that render untenable this diagnosis, made some 150 years after the publication of A Christmas Carol.
First, the osteomalacia evident in RTA type 1 is symmetrical whereas Tiny Tim's crippling disease was asymmetrical. Renal tubular acidosis rarely involves the hands to the extent described in Dickens' famous story. Furthermore, RTA rarely leads to death. I am not aware of any deaths due to RTA, although it is theoretically possible, as indicated in the quotations from Rodriguez-Soriano's article
Pneumonia is the most important cause of morbidity and mortality in children aged under 5 years worldwide. Studies in developing countries have suggested an association between nutritional rickets and pneumonia. Since both nutritional rickets and pneumonia are common in Ethiopia, we did a case-control study to determine the role of nutritional rickets in the development of pneumonia.
Cases were children younger than 5 years admitted to the Ethio-Swedish Children's Hospital during a 5-year period with a diagnosis of pneumonia (n = 521), but data were incomplete for 21 of these and they were not included. Controls (n = 500) were matched for admission within 3 months of cases and age within 3 months and had no evidence of pneumonia. Nutritional, demographic, and clinical and radiographic data for rickets and pneumonia were collected. Matched odd ratios and logistic regression were used to test the significance of the association of rickets and pneumonia.
Rickets was present in 210 of 500 cases compared with 20 of 500 controls (odds ratio 22.11). There were significant differences between cases and controls for family size, birth order, crowding, and months of exclusive breastfeeding (p < 0.05). After correction for these confounding factors by logistic regression, there was still a 13-fold higher incidence of rickets among children with pneumonia than among controls (13.37 [95% CI 8.08-24.22], p < 0.001).
Vitamin D or calcium deficiency may be important predisposing factors for pneumonia in children aged under 5 years in developing countries. Efforts to prevent vitamin D deficiency or calcium supplementation may result in significant reductions in morbidity and mortality from pneumonia in these children.
Chronic metabolic acidosis in distal renal tubular acidosis (RTA) has been implicated in the pathogenesis of enhanced bone resorption and osteopenia, resulting in a loss of bone mineral content. However, histomorphometric and bone densitometric studies of patients who suffered from long-standing distal RTA have rarely been done.
A cross-sectional study to determine the alterations of bone mineral density (BMD) and histology was done in 14 nonazotemic RTA patients (11 females and 3 males) who had never received alkaline therapy before enrolling into this study. The mean age was 32.7 +/- 11.9 years. BMD measurements and transiliac bone biopsy were done in all patients. Blood chemistries, intact parathyroid hormone level, and a 24-hour urine collection for the determination of urinary calcium, phosphate, sodium, and potassium were obtained from the RTA patients at the time of bone biopsy. Data from 28 age-, sex-, and body mass index-matched, normal controls who were residents in the same area were also obtained.
Urinary excretion of calcium was 2.05 +/- 1.59 mmol/day. No patient had hypercalciuria. The serum intact parathyroid hormone level was 15.92 +/- 8.48 pg/mL. RTA patients had lower BMD in most areas when compared with normal controls. There were two patients who suffered from a pathologic fracture at the femur. Bone histomorphometry from RTA patients shows a significantly decreased bone formation rate (0.02 +/- 0.02 vs. 0.07 +/- 0.045 microm(3)/microm(2)/day, P < 0.05), not significantly decreased osteoblastic surface (0.78 +/- 1.03% vs. 2.6 +/- 1.1%) and osteoclastic surface (0.05 +/- 0.03 vs. 0.13 +/- 0.23%), but significantly increased osteoid surface (31.47 +/- 24.52 vs. 5.79 +/- 4.39%, P < 0.05) and osteoid volume (2.95 +/- 3.09 vs. 0.92 +/- 1.05%, P < 0.05) when compared with those of normal controls. There was no difference in osteoid thickness (10.65 +/- 6.10 vs. 8.69 +/- 2.14 microm). Only one distal RTA patient who had a marked increase in osteoid thickness justified the diagnosis of osteomalacia.
This study demonstrates that low bone mass is common in distal RTA patients. Chronic metabolic acidosis results in suppression of bone formation and resorption, which in turn may contribute to the development of low bone mass in distal RTA patients. Although minor elevations in osteoid surface and osteoid volume are found among distal RTA patients, overt osteomalacia is not the predominant bone lesion.
Rickets, a disease of vitamin D deficiency, is rarely confronted by the practicing pediatrician in the United States today. At the turn of the 20th century, rickets was rampant among the poor children living in the industrialized and polluted northern cities of the United States. With the discovery of vitamin D and the delineation of the anti-rachitic properties of cod-liver oil by the 1930s, it became possible to not only treat but also eradicate rickets in the United States. Rickets was a common disease in 17th century England. Frances Glisson's treatise on rickets published in 1650, a glorious contribution to English medicine, described the clinical and anatomic features of rickets in great detail. The exact etiology of rickets had been elusive until the 1920s. During the Glissonian era, rickets was a mysterious disease. By the late 19th and early 20th century, faulty diet or faulty environment (poor hygiene, lack of fresh air and sunshine) or lack of exercise was implicated in its etiology. Animal experiments, appreciation of folklore advocating the benefits of cod-liver oil, and the geographical association of rickets to lack of sunshine were all relevant factors in the advancement of knowledge in the conquest of this malady. In this article, the history of rickets pertaining to the discovery of vitamin D, cod-liver oil, and sunlight is reviewed.
An outbreak of rickets in 1959-1960 among infants under routine health supervision in southern Israel led to analysis of the cases. Of 2,105 children examined in the 3 to 24 months' age period, 96 (4.5 per cent) had clinical rickets and 66 of these (3.1 per cent) had confirmatory radiologic signs. These 66 were studied further. Increased incidence was correlated both with the onset of the rainy season and with difficulties of vitamin D supply to child health centers. It was indicated that a minimum dose of over 150 I.U. daily over the first 7 months of life was necessary for even partial protective effect. Hospitalization was twice as common in the children with rickets as in controls over the first year of life and was caused almost entirely by respiratory and gastrointestinal infections, usually before the rickets was diagnosed. Only one difference was found in the comparison of socioeconomic factors: the 18 rachitic children who had been hospitalized were almost exclusively first born or of very high birth rank (5 and over) in contrast both to the controls and nonhospitalized rachitic children. When 59 initial diagnostic films were classified as "active rickets" (39) and "healed or healing rickets" (20), no significant difference was found between the two groups in average age, seasonal incidence, or vitamin D intake. This finding casts some doubt on the reliability of radiologic criteria of activity and healing when applied to a single film.
There has been disagreement about whether osteomalacia (adult rickets) occurs in adults with type 1 (distal) renal tubular acidosis (RTA1). Therefore, after finding scapular pseudofractures in a patient with RTA1 and Sjögren syndrome, we decided to survey other patients with RTA to learn whether osteomalacia occurred in others and, if it did, whether it was necessarily associated with the presence of Sjögren syndrome.
We examined the hospital records and laboratory findings of 250 patients with codes for RTA, 124 with codes for osteomalacia, and 20 with codes for Sjögren syndrome who were seen at a university-affiliated acute care municipal hospital since 1990. Further detailed survey was then limited to patients older than 15 years and excluded those with potentially confounding causes of bone disease such as chronic renal insufficiency or sickle cell disease. Seven adults with RTA1 were thereby identified.
Two adults with RTA1 had radiological and biochemical findings compatible with osteomalacia, and 1 had findings compatible with Sjögren syndrome. A third patient without Sjögren syndrome had biochemical findings suggestive of osteomalacia.
Osteomalacia seems to occur in some adult patients with RTA1, and not only in association with Sjögren syndrome. We found no biochemical evidence of osteomalacia in the patients with Sjögren syndrome who did not have RTA.
Vitamin D3 is a prohormone produced in skin through ultraviolet irradiation of 7-dehydrocholesterol. It is biologically inert and must be metabolized to 25-hydroxyvitamin D3 in the liver and then to 1alpha,25-dihydroxyvitamin D3 in the kidney before function. The hormonal form of vitamin D3, ie, 1alpha,25-dihydroxyvitamin D3, acts through a nuclear receptor to carry out its many functions, including calcium absorption, phosphate absorption in the intestine, calcium mobilization in bone, and calcium reabsorption in the kidney. It also has several noncalcemic functions in the body. This overview provides a brief description of the physiologic, endocrinologic, and molecular biologic characteristics of vitamin D. It also provides information on new selective analogs of 1alpha,25-dihydroyvitamin D3 for therapy.
