[Bilateral cystoid macular edema after successful treatment of AIDS-associated cytomegalovirus retinitis]. / Bilaterales zystoides Makulaödem nach erfolgreich therapierter AIDS-assoziierter CMV-Retinitis.

BACKGROUND: Cystoid macular edema (CME) in AIDS patients with inactive cytomegalovirus (CMV) retinitis is an uncommon but potentially sight-threatening complication. The pathogenesis of CME in these patients is unclear. This study tries to identify possible risk factors by analyzing the charts of five patients. METHODS: Ten eyes of 5 patients that finally developed CME were followed for an average of 18 months. The initial retinal lesions, their response to antiviral treatment, the development of CME, and the patients' immune status were prospectively monitored. RESULTS: CMV retinitis was diagnosed at a median CD4+ count of 3 cells/mm3 (range 0-11). All eyes responded to the initial systemic anti-viral treatment. At the onset of CME, CMV retinitis was controlled by antiviral maintenance therapy in all patients [ganciclovir (n = 2), cidofovir (n = 2), foscarnet (n = 1)]. The median time between diagnosis of CMV retinitis and onset of CME was 11.5 months (range 5-24). Development of CME was associated with significant visual loss: acuity ranged from 0.05 to 0.7 when CME was first noticed, compared to 0.8-1.25 at diagnosis of CMV retinitis. Duration of inflammation, size or zone of retinal necrosis did not favor the development of CME, neither did the antiviral therapy. A weak correlation of CME development and immune status (expressed as increase of CD4+ cells) was found. Due to systemic corticosteroids CME resolved. CONCLUSIONS: CME is a new visual threat to AIDS-patients with CMV retinitis whose immune status improved under the latest combined antiretroviral therapy. Therapy with oral corticosteroids may positively influence this condition.

[Autoregulation in the choroid]. / Uber die Autoregulation der Aderhaut.

The cerebral perfusion is continuously and highly sensitively dependent on arterial pCO2. Does the ocular perfusion behave in a similar manner? To answer this question, the authors measured the following parameters before and after the inhalation of 10% CO2: a) the increase of capillary pCO2, using a transcutaneous sensor, and b) the redness (pallor) of the retinal tissue, an expression of its hemoglobin content, was measured at two retinal locations with the Ocular Photometer (OPM). Initial results from young test-volunteers and patients with documented carotis stenoses show that the choroid is able to maintain constant its blood-volume even under changing loads.

Effect of coenzyme-A, NAD, alpha lipoic-acid and cocarboxylase on survival of rats with galactosamine-induced severe hepatitis.

Galactosamine, a selective hepatotoxin, produces in rats histologic alterations, which show the characteristics of severe human viral hepatitis. In the present study the efficacy of two different cofactor regimens (coenzyme A, NAD, alpha lipoic-acid, cocarboxylase) in rats with fulminant galactosamine hepatitis were tested. The results showed an improvement of the short-term survival with a short-term treatment and definitely better survival with a long-term regimen with cofactors.

Chronic interstitial nephritis in Whipple's disease.

Report is given on a 68-year-old man who suffered primarily from progressive weight loss and repeated episodes of fever and arthralgia. Later, liver dysfunction and renal insufficiency developed. Liver and kidney biopsies disclosed granulomatous hepatitis and nephritis. Because of the morphologic and clinical findings, the diagnosis of Boeck's disease was made. Shortly before death, diarrhea developed. Autopsy revealed a massive systemic involvement in Whipple's disease proven by light and electron microscopy and immunofluorescence. Tuberculoid and epitheloid cell granulomas and isolated giant cells were found in addition to the biopsy findings in skeleton muscles, the small intestine, lymphnodes and bronchi. At autopsy, the kidney showed chronic interstitial nephritis. The literature of kidney involvement in Whipple's disease is reviewed. This is the first case with granulomatous interstitial nephritis and chronic renal insufficiency in an inadequately treated Whipple's disease.

[Still's disease in adults. 2 case reports]. / Morbus Still des Adulten. Bericht über zwei Fälle.

Two patients with adult Still's disease are presented. Both had high "septic" fever, weight loss, mild pharyngitis, evanescent maculo-papular rash, myalgias, arthralgias, splenomegaly and pericarditis, while one of the two patients also had lymphadenopathy and pleurisy. Arthritis, which is a sine qua non for the diagnosis, developed only 5 months after disease onset in one patient. Both ultimately developed severe destructive joint disease requiring hip arthroplasty. Laboratory findings were neutrophilic leukocytosis, normochromic normocytic anemia, elevated ESR, slightly elevated liver enzyme values, negative IgM-rheumatoid factor and antinuclear antibodies, and normal or slightly elevated complement factors. Several biopsies failed to reveal pathognomonic findings. It is of the utmost importance that the exclusion diagnosis of adult Still's disease be posed in order to avoid repeated hospitalizations with undue investigations and unnecessary therapeutic trials with antibiotics.

Metabolites of glucose in the blood of patients with renal failure.

The blood concentrations of pyruvate and of some of its metabolites and the red cell 2,3-diphosphoglycerate concentration were compared with the severity of uraemia in 103 patients with renal failure. In chronic renal failure 2,3-butylene glycol was distinctly elevated, and a positive linear correlation (2p Less Than 0.001) with the urea was found. The values were even higher in corresponding patients with uraemic pericarditis, but,--taking into account their relation to the urea--,they were not elevated in acute renal failure. Acetaldehyde, acetoin and acetate behaved in part likewise. Severe uraemia, which clinically was demonstrated by uraemic pericarditis, was characterized biochemically, without regard to the urea, by very elevated values of 2,3-butylene glycol and acetaldehyde and of the pyruvate: lactate ratio. In addition, the chronic patients who were not undergoing regular haemodialysis, did not show the expected rise of 2,3-diphospho-glycerate along with progressive anaemia. The data suggest that the uraemic state is characterized by the impairment of the oxidative glucose metabolism between pyruvate and the tricarbonic acid cycle more precisely than by the blood urea.

Feedback activation in rat nephrons by sera from patients with acute renal failure.

Tubuloglomerular feedback (TGF) may be triggered by varying the distal electrolyte load. TGF may contribute to acute renal failure (ARF), but maximal TGF stimulation induces only relatively small alterations in single nephron GFR (SNGFR) and stop-flow pressure (SFP), whereas in ARF, GFR may cease, raising the possibility that substances eliciting greater TGF responses than do elelectrolytes occur in ARF. We have sought such substances in serum, urine, and peritoneal fluid from patients with ARF. Sera samples from 1 healthy subject, 4 ARF patients, and 2 other anuric patients were dialyzed against glucose to reduce electrolyte concentrations and perfused through Henle's loops in salt-deplete rats. With ARF sera, SFP fell from 35.6 +/- (SD) 3.5 to 20.9 +/- 3.4 mm Hg (P less than 0.005) and SNGFR from 28.5 +/- 8.7 to 12.6 +/- 7.3 nl/min (P less than 0.005). Furosemide (10(-4) M) did not abolish the response. Perfusion with other patients' sera had no effect on SFP. ARF urine or peritoneal fluid induced similar responses. Conclusion. In some ARF patients, substances present in serum activate TGF in the rat. These substances might contribute to development of certain forms of human ARF, particularly ARF associated with liver dysfunction (hepatorenal syndrome).

Treatment of fulminant hepatic failure with infusions of Co-factors and mannitol and charcoal-hemoperfusions during Forty-one days.

The clinical course of a 26 year old female patient with acute liver necrosis and coma due to hepatitis B is reported. The disturbances of conciousness had improved. The patient survived 41 days after the beginning of the coma and developed liver cell regeneration and an acute post-hepatitic liver cirrhosis. As a grave complication a septicemia with aspergillus was observed. The patient died because of gastro-intestinal hemorrhage. At autopsy there were no signs of brain edema. The treatment consisted in: daily infusions with coenzyme A, nicotinamid-adenin-dinucleotide, alpha lipoic acid and cocarboxylase to improve the metabolic disorders and the clinical picture; mannitol intravenously to prevent and to treat cerebral edema; 33 charcoal-hemoperfusions to remove toxic substances of acute liver failure. Treatment of the aspergillus infection with 5-fluorocytosine and amphotericine B and infusion of concentrated ascites led to a decompensation of liver functions. From this observation the following conclusions can be drawn: after an acute viral hepatic necrosis, new synthetic functions and improvements of the disturbed intermediary metabolism in regenerated liver-cells can eventually be seen only after twenty-four to thirty days. With systematically applicated mannitol infusions it is possible to treat cerebral edema effectively.

Systemic karyomegaly associated with chronic interstitial nephritis. A new disease entity?

In 3 patients, two 26 and one 29 years of age, a nephropathy was accidentally discovered which progressed to end stage renal failure within 4 to 6 years. Renal biopsy revealed an unusually marked karyomegaly particularly of the tubular epithelium. These cytopathological changes were associated with chronic interstitial nephritis. Biopsies of other organs, i.e. liver, colon, bronchus and lungs indicated in 2 patients a systemic distribution of the karyomegaly, particularly in mesenchymal cells. Neither the chronic interstitial nephritis nor the karyomegaly could be ascribed to a recognized etiology. This suggests, therefore, that there is a relationship between these changes. The karyomegaly could be the result of the action of some antimitotic agent such as chemical toxins or virus infections.

Cerebral edema in the rat with galactosamine induced severe hepatitis.

With D-galactosamine hydrochloride severe hepatitis was induced in rats and the water content of cerebrum, cerebellum and brain stem determined. The animals showed a parallel increase in cerebral water content and occurrence of cerebral symptoms.

On the mechanism of action of biguanides. evidence against an inhibition of gluconeogenesis from protein in normal fasting subjects.

The effect of phenformin on fuel homeostasis and on gluconeogenesis from protein was studied in 8 normal subjects who underwent two 4-day fasts 8-12 weeks apart. Each person received placebo or phenformin 50 mg every 12 hours for 3 days before and during the fasts. Circulating glucose, lactate, pyruvate, free fatty acid and ketone levels as well as urinary nitrogen excretion observed during placebo and phenformin treatment were not significantly different from each other. The lack of an effect of phenformin on urinary nitrogen excretion and plasma glucose level strongly suggests that gluconeogenesis from amino acids was unaltered by phenformin in these fasting subjects. The present findings are at variance with those by other authors which may be related to differences in methodology.

[Carbohydrate intolerance during complete fasting]. / Kohlenhydratintoleranz bei vollständigem Fasten.

In the first part of the study oral glucose tolerance tests (GTT) or insulin tolerance tests (ITT) were performed in 22 lean and 22 obese nondiabetics before and after fasts of at least 6 days' duration. Deterioration of glucose tolerance was greater in lean than in obese individuals. Plasma levels of factors known to influence glucose tolerance (glucagon, growth hormone, free fatty acids, ketones) were significantly higher in fasting lean than in fasting obese subjects. Furthermore, delayed insulin rise (GTT) and decreased insulin sensitivity (ITT) were observed after starvation in lean subjects but not in the obese, which could explain the greater deterioration of glucose tolerance in the lean population. In the second part of the study glucose and fructose tolerance were compared during 4-hour infusions of these substrates (0.5 g/kg/h) in 8 normal subjects before and after two 4-day fasts. After starvation, glucose as well as fructose infusion resulted in plasma levels of the infused hexose significantly higher than in control, and the rise in plasma lactate and pyruvate was delayed. These results contradict the view widely held in the literature, that fructose metabolism remains unimpaired in the fasting state.

Comparison of glucose and fructose tolerance before and after starvation.

Glucose and fructose were studied in eight healthy volunteers who fasted twice for 4 days. Before and after the fasts each subject received a 4-hr glucose or fructose infusion providing 0.5 g/kg/hr. Glucose infusion during starvation resulted in a mean maximal plasma glucose rise of 401 +/- 21 mg/100 ml (+/- SEM) as compared to 119 +/- 10 mg/100 ml before starvation. Insulin/glucose ratios were lower than normal in fasted subjects. Fructose infusion during fasting produced a maximal plasma glucose rise of 91 +/- 9 mg/100 ml as opposed to 5+/-1 mg/100 ml before starvation. During fructose infusion in the fasted state, plasma fructose levels were higher than control and the rise in blood lactate and pyruvate was delayed, but finally lactate concentrations were above control values. The antiketotic effects of intravenous glucose and fructose were similar during fasting but fructose was significantly less potent in reducing free fatty acid levels. After starvation, urinary carbohydrate losses during glucose infusion were 5 times higher than those observed during fructose infusion. Thus, fructose utillization was less impaired during fasting than was glucose utilization, although fasting induced abnormalities in both glucose and fructose metabolism.

[Elementary diet as an alternative to parenteral feeding in severe gastrointestinal diseases]. / Elementaire Diät als Alternative zur intravenösen Ernährung bei schweren gastrointestinalen Krankheiten

21 patients with gastroenterological disease and indication for the use of intravenous nutrition received an elemental diet (ED) for 5-44 days. In 6 out of 8 patients with exacerbation of Crohn's disease remissions were achieved, apart from 3 persistent fistulas. In 5 out of 9 cases with various primary diseases and postoperative intestinal fistulas, spontaneous healing was observed. Furthermore, 2 patients with ulcerative colitis, 1 with radiation enteritis and 1 with pancreatitis were treated with ED. On ED, hemoglobin increased from 11.3 +/- 0.4 (m +/- SEM) to 12.0 +/- 0.5 g% (p less than 0.01) and serum albumin from 2.7 +/- 0.1 to 3.4 +/- 0.1 g% (p less than 0.001). Nitrogen requirements were studied in 11 patients receiving various quantities of ED. Nitrogen balance was found to be in equilibrium or positive in 7 patients, and negative in 4. In one patient with severe ulcerative colitis, fecal nitrogen losses were higher than urinary nitrogen losses. The unpleasant taste of ED resulting from free amino acids limited the ED supply in 3 patients and led to premature ending of ED administration in 3 other patients. In such cases ED may be given by nasogastric tube feeding. From the results presented it appears that ED is indicated in Crohn's disease and intestinal fistulas. However, the results obtained require confirmation by further observations and comparison with an intravenously fed control group.