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The treatment of broken bones has long adhered to principles of tight juxtaposition of fracture ends and of strict rest. Splinting and casting with plaster of Paris helped considerably. Attempts at internal splinting with pegs, bolts, or stabilizing contraptions usually failed. Foreign materials were either not biocompatible or broke easily, and the insertion of these prostheses directly into the fracture created additional risks from infections. All this changed when Gerhard Küntscher (1900-1972) stabilized broken long bones by intramedullary insertion of stainless steel nails through a small incision, distant from the fracture. Küntscher employed his method from the late 1930s on, initially as a surgeon at the Kiel University in Germany. His early and encouraging results were rejected when presented in 1940, and he remained ostracized thenceforth. During WWII he was stationed in Finland, where he treated wounded soldiers from both sides of the front. POWs returning home propagated the new method by revealing these rods in roentgenograms of their legs; had he not been so successful in treating POWs, he might have had to stand trial at the Nuremberg Doctors' Trial (1947). He documented his experiments and experiences in more than 200 articles and three monographs. Today, his method is employed universally.

The acute porphyrias, 4 inherited disorders of heme biosynthesis, cause life-threatening attacks of neurovisceral symptoms that mimic many other acute medical and psychiatric conditions. Lack of clinical recognition often delays effective treatment, and inappropriate diagnostic tests may lead to misdiagnosis and inappropriate treatment. We review the clinical manifestations, pathophysiology, and genetics of the acute porphyrias and provide recommendations for diagnosis and treatment on the basis of reviews of the literature and clinical experience. An acute porphyria should be considered in many patients with unexplained abdominal pain or other characteristic symptoms. The diagnosis can be rapidly confirmed by demonstration of a markedly increased urinary porphobilinogen level by using a single-void urine specimen. This specimen should also be saved for quantitative measurement of porphobilinogen, 5-aminolevulinic acid, and total porphyrin levels. Intravenous hemin therapy, started as soon as possible, is the most effective treatment. Intravenous glucose alone is appropriate only for mild attacks (mild pain, no paresis or hyponatremia) or until hemin is available. Precipitating factors should be eliminated, and appropriate supportive and symptomatic therapy should be initiated. Prompt diagnosis and treatment greatly improve prognosis and may prevent development of severe or chronic neuropathic symptoms. We recommend identification of at-risk relatives through enzymatic or gene studies.

Although the biosynthetic pathway to heme has been well elucidated and errors along that route have been identified and firmly connected to specific diseases, the porphyrias, slight but nonspecific abnormalities, are occasionally invoked as proof of porphyria or in support of other diagnoses. An errant patient with a conundrum of symptoms but without an explanation for them might have to take iatrogenic detours only to learn after what are at times ulyssean vagaries that the initial diagnosis of porphyria is in the end untenable. Thus the porphyrias are superb examples of the interface between laboratory and clinical medicine, in which the occurrence of the Ulysses syndrome can be curtailed through the careful ordering of tests and cogent interpretation of their results.

Historical evidence has been collected attempting to diagnose members of royal houses, perhaps most publicized by Macalpine and Hunter (1969) for George III and his assumed porphyria, claiming that his insanity was a classic case of thereof. This rare metabolic disease presents with a variety of signs and symptoms: skin disease, abdominal pain, tachycardia, and neuro-psychiatric findings. The porphyrias are hereditary and since George III and Frederick William I share ancestors it seemed reasonable to investigate if the latter may also have suffered from porphyria. The pathography of both kings is meticulous, showing for both that abdominal pain, erratic behavior, restlessness, and discolored urine were frequently observed and complete recovery interictally was common. Intercurrent illnesses, fasting, alcohol and even tobacco smoking have been shown to be inducers of attacks and these risk factors are well documented in royal history.--The diagnosis of porphyria was not recognized then and other names were used, such as Cachexia hypochondriaca, Asthma spasmodico flatulentum, dolores arthritici.--We propose that Frederick William I suffered from an inducible porphyria.

Porphyrias are relatively uncommon inherited or acquired disorders in which clinical manifestations are attributable to a disturbance of heme synthesis (porphyrin metabolism), usually in association with endogenous or exogenous stressors. Porphyrias are characterized by elevations of heme precursors in blood, urine, and/or stool. A number of chemicals, particularly metals and halogenated hydrocarbons, induce disturbances of heme synthesis in experimental animals. Certain chemicals have also been linked to porphyria or porphyrinuria in humans, generally involving chronic industrial exposures or environmental exposures much higher than those usually encountered. A noteworthy example is the Turkish epidemic of porphyria cutanea tarda produced by accidental ingestion of wheat treated with the fungicide hexachlorobenzene. Measurements of excreted heme precursors have the potential to serve as biological markers for harmful but preclinical effects of certain chemical exposures; this potential warrants further research and applied field studies. It has been hypothesized that several otherwise unexplained chemical-associated illnesses, such as multiple chemical sensitivity syndrome, may represent mild chronic cases of porphyria or other acquired abnormalities in heme synthesis. This review concludes that, although it is reasonable to consider such hypotheses, there is currently no convincing evidence that these illnesses are mediated by a disturbance of heme synthesis; it is premature or unfounded to base clinical management on such explanations unless laboratory data are diagnostic for porphyria. This review discusses the limitations of laboratory measures of heme synthesis, and diagnostic guidelines are provided to assist in evaluating the symptomatic individual suspected of having a porphyria.

Acute intermittent porphyria (AIP) is a genetic disorder in which patients may have life threatening attacks of neurologic dysfunction. This study examined the prognosis during the past 50 years of patients in the United States who required hospitalization for porphyric attacks. The cumulative survival was determined for 136 patients with AIP who were hospitalized for porphyric attacks between 1940 and 1988. Diagnosis was established on the basis of clinical symptoms, in combination with increased urinary excretion of porphobilinogen. The patient group had an average age of 32 years (range 9 to 75) at diagnosis and consisted of 43 males and 93 females. At follow-up, 19 males (44%) and 31 females (33%) were decreased. The standardized mortality ratio for the 136 patients, compared to an age-matched hypothetical population experiencing USA 1970 Census Death Rates was 3.2, with a 95% confidence interval of 2.4-4.0. Most deaths occurred during the initial porphyric attack (20% of deaths) or a subsequent attack (38% of deaths). Suicide was also common (five deaths). Comparison was made between 50 patients who were diagnosed before 1971, the year in which hematin therapy became available, and 86 patients who were diagnosed afterward. There was improved survival in the latter group, particularly after 10 years from the time of diagnosis, but this did not reach statistical significance. In conclusion, the proportionate increase in mortality due to symptomatic AIP was three-fold compared to the general population during the past 50 years. The major cause of the increased mortality was the porphyric attack itself.

William Osler, considered one of the preeminent American physicians at the turn of the century, studied in North America and in Europe. His later influence in molding the teaching and the specialty of internal medicine is still felt. One may ask to what extent his ideas were generated or influenced by his extensive German experiences? Most certainly his exposure to pathology in Germany was profound and lasting. While there can be no doubt that Osler was a Germanophile throughout his career, one has to conclude that his academic influences were more English and not exclusively German. He was cosmopolitan and used and promulgated good ideas wherever he found them.

The development of Bad Nauheim, a German spa that over 2 centuries became dominant in the attraction of patients with heart disease is described. Here, patients experienced a regimen of saline baths and mostly static exercises developed by the Schotts, 2 physician brothers. Concomitant with the bathing and exercises, there was a social atmosphere conducive to relaxation. Many visiting physicians were impressed that there were improvements in the patients' cardiac status. One skeptical exception was Sir James Mackenzie, whose views are synopsized. The reported improvements may have had a modicum of a physiologic base, from recent investigations on the nature of heart failure, and may have anticipated the current use of exercise in cardiac rehabilitation.

Background: Variegate porphyria is a genetic disorder of porphyrin metabolism in which patients may have both neurologic dysfunction and photocutaneous lesions. Biochemical confirmation of the diagnosis can be difficult, particularly in patients without neurologic dysfunction at the time of testing. The demonstration of increased fecal excretion of porphyrin is frequently used for this purpose, but levels may be normal. Since elevated fecal porphyrin levels in variegate porphyria are presumably a consequence of increased biliary excretion, we evaluated whether analysis of porphyrins in bile distinguishes better between patients with variegate porphyria and controls., Methods: Bile samples were collected by duodenal aspiration from 10 patients with proved variegate porphyria who had no neurologic symptoms when they were studied and 17 control subjects. Bile and fecal porphyrin levels were measured fluorometrically., Results: The mean total porphyrin concentration in bile in the patients with variegate porphyria was significantly higher than that in the controls (67.8 vs. 0.71 mumol per liter; P less than 0.00002). There was more than a ninefold difference between the highest level in any control subject and the lowest level in any patient with variegate porphyria. The mean fecal porphyrin level in the patients with variegate porphyria also differed significantly from that in the controls (0.79 vs. 0.14 mumol per gram of dry weight; P less than 0.007), but four patients had levels within the control range., Conclusions: The concentration of porphyrin in bile is higher in patients with variegate porphyria than in controls, and the difference is greater than that for fecal porphyrin. Bile porphyrin measurements may be helpful in the evaluation of asymptomatic patients suspected of having variegate porphyria.