[Development and consequences of physician shortages in Bavaria]. / Entwicklung und Konsequenzen des Arztemangels in Bayern.

AIM: Germany's growing shortage of doctors is a current topic of numerous discussions in healthcare policy. The objective of this study is to show the medical supply situation and migratory movement of doctors in the outpatient and inpatient physician care sector, with particular emphasis on the immigration of foreign doctors to Germany and its consequences. SUBJECTS AND METHODS: The annual statistical reports from the Bavarian Medical Association and the Federal Medical Association were investigated with regard to foreign doctors and migratory movements. To establish Bavaria's situation regarding outpatient physician care, unpublished case reports and planning sheets of the Statutory Health Insurance Physicians in Bavaria (KVB) were analysed. A survey amongst Bavarian hospitals shows the current situation of the inpatient care sector. RESULTS: The trend of emigration by German doctors continues unabated, especially to Switzerland, UK, USA and Austria. In Bavaria, outpatient care by GPs or specialists is still standard or in oversupply. However, the survey was able to confirm a considerable lack of doctors for inpatient care. So far, it has been possible to compensate existing staff shortages in hospitals by employing foreign doctors, despite significant language deficits. DISCUSSION AND CONCLUSIONS: To resolve the shortage of doctors in future, a reform of the Medical Requirements Planning in combination with structural improvements and measures to integrate immigrant doctors is essential.

Inguinal hernia vs. arthritis of the hip in sporting adolescents--case report and review of the literature.

UNLABELLED: Chronic pain in the hip, groin or thigh can be caused by a wide spectrum of diseases posing extended diagnostic problems. We describe the case of a 10-years old child with chronic pain in the groin with gait restriction for more than six months without successful classification and treatment. The girl suffered from heavy pain in the groin after a sporting contest which forced her to walk with walking sticks and to avoid climbing stairs. Within six months she was examined by pediatric, orthopedic, pediatric surgery, pediatric orthopedic, radiology, pediatric rheumatology specialists. Working diagnoses were transient synovitis (coxitis fugax), arthritis, streptococcal arthritis, Morbus Perthes, rheumatic fever, rheumatoid arthritis. She was treated with antibiotics and ibuprofen in high dosage. Repeated laboratory tests and imaging studies (ultrasound, x-rays, magnetic resonance imaging) of the hip and pelvis did not support any of these diagnoses. Six months after beginning of the complaints the girl was presented by her mother to our institution. The physical examination showed a sharp localized pain in the groin, just in the region of the inguinal ligament with otherwise free hip movement. There was no visible inguinal hernia. The family history for hernia was positive. After infiltration of the ilioinguinal nerve the girl had a complete long-lasting disappearance of pain and gait disturbance. This led to the diagnosis of inguinal hernia with nerve entrapment. After hernia repair and neurolysis/neurectomy there was a continuous state of disappearance of pain and gait disturbances. CONCLUSION: To avoid such a diagnostic dilemma one should always discuss all possible causes. Non-visible inguinal hernia may be more common in females than previously thought. Nerve entrapment as a cause of groin pain has been well described. The relationship of the start of complaints with sporting activity, a positive family history for inguinal hernia, a lack of signs of inflammation and bone involvement in the laboratory and imaging studies together with a localized pain in the groin, almost immediate long-lasting disappearance of pain after infiltration of the ilioinguinal nerve allowing free motion leads to the diagnosis of inguinal hernia with nerve entrapment. Hernia repair and neurolysis are the adequate treatment avoiding unnecessary radiation.

Lunar phase does not influence surgical quality.

INTRODUCTION: 10.5% of the German population believes in the effects of lunar phase on disease. The topic is hot in German TV program. It is believed that at new moon the rate of bleeding complications is increased and operations during the waning phase of the moon would be best to avoid complications, pain and scaring. To our knowledge the effect of lunar phase has not been studied in ambulatory surgery. PATIENTS AND METHODS: 782 patients were evaluated for complications and perception of the personal health after herniotomy, haemorrhoidectomy and crossectomy with partial vein stripping with or without phlebectomy as part of a quality control study. A questionnaire has been sent out to the patients asking the patient to rate postoperative pain, pain medication, restriction of daily activity, mental health and emotion, status of complaints after the operation. RESULTS: In 782 patients (mean age 50 years) 866 operations were performed. There were no major complications and only in 3.71% minor complications (local bleeding, haematoma, inflammation, abscess, seroma, lymphatic fistula, dehiscence) were observed. The operations were equally distributed to the lunar phases. Complications and patient's subjective perception of pain, restriction of daily activity, mental health and emotion, status of complaints after the operation were not associated with a lunar phase. CONCLUSIONS: The hypothesis that lunar phase influences the outcome of ambulatory operations is not valid. With regard to the organization of operations in the hospital and the patient's uncertainty to decide the right time the lunar phase philosophy may have an socio-economic impact not yet understood.

Amoxicillin-clavulanic acid therapy may be associated with severe side effects -- review of the literature.

INTRODUCTION: There is a growing body of evidence that amoxicillin-clavulanic acid may induce severe adverse effects in patients. METHODS: A medline search of case reports and reviews on amoxicillin-clavulanic acid induced adverse effects was performed. The criteria of a consensus conference on the reporting of drug-induced liver disease were applied. RESULTS: Amoxicillin-clavulanic acid has been associated with drug-induced cholestatic hepatitis in 208 reported patients. In 153 evaluable patients there were 106 males and 47 females with a mean age of 60 years (1-90). Liver associated co-morbidity and co-medication does not play a major part in the development of disease. In most instances respiratory tract infection and sinusitis were treated by amoxicillin-clavulanic acid with a mean treatment duration of 13.9 days and a reaction time until first onset of jaundice of 25.2 days average. Infection and cholestasis from other reason were ruled out in most patients. Liver injury was classified according to laboratory parameters to be hepatocellular in 35 patients, cholestatic in 24 patients and mixed in 83 patients. Normalization of liver enzymes was observed 11.5 weeks after onset of drug administration (average); three of 153 patients did not survive the adverse event. CONCLUSION: Amoxicillin-clavulanic acid which is marketed for treatment of respiratory infections and sinusitis/otitis may in some cases induce severe adverse effects and death in patients of different age, especially if they are on multidrug regimens. In consideration of this fact many authors recommend to reflect carefully, whether amoxicillin-clavulanic acid is necessary in treatment of patients with localized or uncomplicated infections. If amoxicillin-clavulanic acid is prescribed, transaminase, alkaline phosphatase and bilirubin tests should be obtained within the first two weeks and after four to five weeks after beginning of treatment to recognize early enough undesired hepatic side effects.

Effect of ribose on cardiac adenine nucleotides in a donor model for heart transplantation.

Preservation time of explanted hearts is short. Cardiac function after transplantation declines dramatically in hearts that have been preserved for more than 4 to 6 hours. This has been linked to a critical decrease in high energy phosphates (HEP) after explantation. Ribose has previously been shown to stimulate HEP synthesis and to improve cardiac function. In this study, ribose was infused into 20 rats for 24 hours continuously before explantation (donor treatment) and also added to the solutions used for preservation. Saline was used in the control group. Myocardial tissue biopsies were taken after 24h of infusion and after 4h of preservation. High energy phosphates were determined by HPLC. Adenosine triphosphate content (ATP), energy charge and total adenine nucleotides (TAN) were significantly lower after 4h of preservation in both the ribose-treated and the control group compared to hearts before preservation. The difference in mean ATP concentrations between the 4 hours preserved ribose group and the control group was not significant. Single case analysis however revealed a minimum ATP level of 12.3 micromol/g dry weight in 10 ribose treated hearts whereas 2 out of 11 control hearts showed ATP levels below 10 micromol/g dry weight. - This study supports the hypothesis that ribose treatment is capable of maintaining ATP at a higher level in preserved rat hearts. Donor treatment and metabolic support with ribose during organ preservation may be suitable to prolong preservation time of donor hearts.

Three missense mutations in the galactose-1-phosphate uridyltransferase gene of three families with mild galactosaemia.

UNLABELLED: Classical galactosaemia caused by deficiency of galactose-1-phosphate uridyltransferase (GALT) is characterized by acute symptoms of hepatocellular dysfunction, sepsis, cataracts and failure to thrive. Galactose limitation reverses these complications immediately, however, most of these children have a long-term complication of verbal dyspraxia mental retardation and ovarian failure. The GALT gene was cloned and several mutations including the common Q188R have been reported. In this study the coding region of GALT was amplified by polymerase chain reaction from genomic DNA of classical galactosaemic individuals and characterized by direct sequencing of the products. Three missense mutations were identified in three patients with a mild galactosaemic variant: (1) replacement of threonine-138 by methionine (T138M); (2) replacement of arginine by tryptophan (R259W); and (3) replacement of threonine by alanine (T350A). All three galactosaemic individuals, one girl and two boys, have varying degrees of residual GALT activity in RBC and their galactose-1-phosphate levels decreased much faster than in other galactosaemic patients. These missense mutations occur in regions that are not highly conserved domains. CONCLUSION: The study of the molecular basis related to the phenotype variation may indeed help to prognosticate the outcome of patients with classical galactosaemia.

Molecular characterization of Duarte-1 and Duarte-2 variants of galactose-1-phosphate uridyltransferase.

The N314D polymorphism was found in two different alleles of the galactose-1-phosphate uridyltransferase (GALT) gene, Duarte-1 (D1) and Duarte-2 (D2). Although both variants have identical electrophoretic mobility and isoelectro-focusing points, the galactose-1-phosphate uridyltransferase (GALT) activity varies: D1 alleles showed 110-130% of the normal RBC activity, but D2 alleles only 40-50%. We found that D1 alleles also carried a silent mutation in exon 7 (L218L) in addition to N314D. In contrast, besides N314D, D2 alleles carried two regulatory mutations, G1105C and G1391A, in introns D and E, respectively. In normal and Q188R alleles none of the above four mutations coexisted. However, some galactosaemia alleles with mutations other than Q188R, such as W316X and E340X of exon 10, also carried the N314D mutation. The W316X alleles existed in cis with the intron mutations (G1105C and G1391A), whereas those with E340X are in cis with L218L. In all cases examined, the intron mutations were not found in D1 alleles and no D2 alleles had the silent mutation of L218L. These results suggest that the decrease in the GALT activity in D2 may be due to regulation of the GALT gene expression. The G1105C site may be critical to the function of erythroid transcription factor NF-E1, since it flanks the core consensus sequence for one of its binding sites. The G1391A mutation may affect another cis-acting regulatory sequence. Alternatively, both mutations may be involved in an aberrant splice processing, which possibly results in a low level of correctly spliced mRNA.

Characterization of two stop codon mutations in the galactose-1-phosphate uridyltransferase gene of three male galactosemic patients with severe clinical manifestation.

Classical galactosemia, which is caused by deficiency of galactose-1-phosphate uridyltransferase, is characterized by acute problems of hepatocellular dysfunction, sepsis, cataracts and failure to thrive. Galactose limitation reverses these symptoms immediately; however, the long-term complications, such as mental retardation and ovarian failures are major problems in most of these patients. In order to investigate the molecular basis for phenotype variation in galactosemia, we have screened the most common mutation in the GALT gene, Q188R. We have further examined those patients who are heterozygous for Q188R or negative for this mutation by SSCP analysis and direct sequencing. In three male patients, we have identified, for the first time, two stop-codon mutations in the GALT gene, G212X (exon 7) and E340X (exon 10). Two patients of 8 and 28 years of age, respectively, who are compound heterozygotes for Q188R and G212X, have severe mental retardation and their general clinical condition is more severe than that of patients with missense mutations. The third patient, who is 8 years of age and who is homozygous for E340X, the N314D polymorphism and a silent substitution L218L, presents with a relatively normal physical and mental condition to date.

Capillary electrophoresis for screening of adenylosuccinate lyase deficiency.

We report a new screening method for adenylosuccinate lyase (ASase) deficiency using capillary electrophoresis (CE). This enzyme defect causes secondary autism and psychomotor retardation in early childhood. In all body fluids of these patients, two succinylpurine metabolites can be found that are normally not detectable: succinyladenosine and succinylaminoimidazole carboxamide (SAICA) riboside. A Beckman P/ACE 2050 capillary electrophoresis system was used with a 47.1 cm capillary, 75 microns ID, and the P/ACE Beckman UV absorbance detector. Untreated urine, injected for 1 s, was separated in a pH 8.63 borate buffer at 20 kV. The two succinylpurines (migration times 13.36 and 13.60 min) were detected at 254 nm only in urine of patients with ASase deficiency but not in control samples.

Deposits of paraprotein in small vessels as a cause of skin ulcers in Waldenström's macroglobulinemia.

A 71-year-old man presented with epistaxis and large ulcers on arms and legs. A monoclonal IgM-kappa gammopathy and high levels of cryoglobulins were found. Histology of the affected skin showed deposits of paraprotein in the small vessels, causing luminal obstruction. This in turn caused ischemic skin lesions, which were successfully treated with cortisone (fluocortolone 100 mg/day every second day) and cyclophosphamide (100 mg/day).

Benzbromarone hydroxylation in man: defective formation of the 6-hydroxybenzbromarone metabolite.

To determine the elimination phenotype of the uricosuric agent benzbromarone 100 mg of the drug was administered as a single oral dose to 11 volunteers on a formula diet; plasma concentration-time profiles of the parent drug and the main metabolites M1 (1'-hydroxybenzbromarone) and M2 (6-hydroxy-benzbromarone) were measured by high-performance liquid chromatography for 168 h. Of the 11 subjects 2 showed higher plasma concentrations and delayed elimination of benzbromarone and metabolite M1 but reduced formation of metabolite M2 compared to the other 9 subjects. However, the plasma concentration-time profiles of the metabolites in these two slow eliminators, termed type 2, differed from those of a poor eliminator characterized during a previous study; the latter, termed type 1, eliminated benzbromarone as well as both metabolites M1 and M2 slowly. The differences in the elimination of benzbromarone and its metabolites are probably caused by differences in the activities of the cytochrome P450 mono-oxygenase isozymes. The results show that determination of the phenotype solely by measurement of the 24-h benzbromarone plasma concentration does not unequivocally characterize slow benzbromarone eliminators; additional plasma concentration-time profiles of the parent drug and metabolites are necessary. Metabolite M2 is characterized as 6-hydroxybenzbromarone; the formation and elimination of the chiral metabolite M1 is enantioselective.

Ergometer exercise in myoadenylate deaminase deficient patients.

Three patients with primary myoadenylate deaminase deficiency were subjected to exercise on a bicycle ergometer at 125 W for 30 minutes. Blood samples prior to, during, and at the end of exercise were analyzed for lactate, ammonia, and hypoxanthine. In addition, urinary hypoxanthine excretion was measured. In these patients the serum lactate level increased to concentrations between 7.9 and 9.0 mmol/l at the end of exercise whereas the mean lactate level in nine control subjects at the end of exercise was 3.3 mmol/l (range 1.1-8.1 mmol/l). There was no difference to control subjects in the exercise-induced increase in plasma levels of ammonia and hypoxanthine or in the increase in urinary hypoxanthine excretion. The findings support the hypothesis of a reduced substrate supply to the citric acid cycle in myoadenylate deaminase deficiency. The normal formation of ammonia and hypoxanthine excludes a marked loss of adenine nucleotides in working muscles in these patients.

Relapsing polychondritis presenting as cutaneous polyarteritis nodosa.

Relapsing polychondritis is an infrequently diagnosed, though not necessarily uncommon, systemic disorder characterized by recurrent and potentially destructive inflammation of cartilaginous structures, the eye, and the audiovestibular and cardiovascular systems. Although dermal involvement occurs in approximately 25% of patients with relapsing polychondritis, in only few cases has a skin biopsy been obtained revealing lesions such as leukocytoclastic vasculitis, livedo reticularis, erythema nodosum or keratodermia blenorrhagicum. We describe a patient with relapsing polychondritis in whom a cutaneous polyarteritis nodosa preceded cartilage inflammation by 6 months. Cutaneous polyarteritis nodosa is a rare form of vasculitis that appears to be limited primarily to the skin, muscles, and joints. In contrast to the systemic form of the disease it is characterized by the absence of visceral lesions and a relapsing but benign course. The present case and the fact that vasculitis is a concomitant feature in approximately 30% of patients with relapsing polychondritis [21] demonstrates that this condition may not represent a distinct clinical entity.

Allopurinol and oxypurinol in human breast milk.

To pregnant or breast feeding women drugs should be given with caution. We report the case of a 5-week-old breast-fed infant whose mother was taking 300mg allopurinol/day for 4 weeks. Allopurinol and oxypurinol were detected by HPLC in maternal plasma and breast milk with a method first described here. In infant's plasma taken 2 h after breast feeding oxypurinol was found; allopurinol was below the limit of detection. The milk/plasma ratio in the mother 2 h (4 h) after drug ingestion was 0.9 (1.4) for allopurinol and 3.9 (2.4) for oxypurinol. The average daily dose for the baby of allopurinol was 0.14-0.20 mg/kg and that of oxypurinol 7.2-8.0 mg/kg by ingestion of breast milk after oral intake of allopurinol by the mother.

GM-CSF and G-CSF in Felty's syndrome.

The risk of infection is increased in patients with Felty's syndrome, neutropenia being one of the main reasons for the susceptibility to infection. We report the case of a 56-year-old patient with Felty's syndrome in whom successive therapy with GM-CSF, splenectomy, and G-CSF was tried because of recurrent severe infections. Therapy with GM-CSF and G-CSF resulted in improvement of neutropenia and in successful treatment of cutaneous and pulmonary infections.