Treatment of Patients with Systemic Lupus Erythematosus including Nephritis with Chlorambucil

Six female patients with systemic lupus erythematosus (S.L.E.) have been treated with chlorambucil. In five the decision was taken after failure by corticosteroids to control progressive renal disease in the face of unacceptable corticosteroid toxicity. After the introduction of chlorambucil renal function improved and all patients remain well six, six, five, three, and two-and-a-half years later, respectively. On renal biopsy five had focal proliferative glomerulonephritis. Repeat biopsy in two cases showed quantitative improvement. The sixth patient was treated with chlorambucil because of failure by corticosteroids to control peripheral vascular lesions and haemolysis and she remains well four years later. In four patients is it probable that amenorrhoea was related to chlorambucil treatment, but there were no other important side effects although one patient developed a degree of marrow depression during treatment. Chlorambucil may hold advantages over the immunosuppressive drugs normally recommended in this condition, azathioprine and cyclophosphamide, as it appears less liable to cause important marrow suppression and, unlike cyclophosphamide is not associated with alopecia and haemorrhagic cystitis.     

Haemolytic anaemia after cisplatin treatment.

Normochromic or normocytic anaemia is a common side effect of treatment with cisplatin. Two patients treated with cisplatin 100 mg/m2 in combination with vinblastine, bleomycin, and actinomycin D developed haemolytic anaemia. Neither patient had evidence of haemolysis before treatment, and in both cases severe haemolytic anaemia developed after several courses of cisplatin and when the cancer had regressed almost completely. The importance of haemolysis in the development of anaemia after cisplatin treatment has not been investigated fully and further studies are needed.     

Red Cell Survival after Heterograft Valve Surgery

Intravascular haemolysis was studied in 24 patients three to nine months after calf or pig valve heterografts had been inserted for severe valvular heart disease. No patient had haemolytic anaemia. In five of the 24 patients there was subclinical haemolysis, and in these five the haemolysis appeared to be related to residual aortic regurgitation or to the presence of other foreign material such as a Dacron aortic graft. The extent of postoperative haemolysis in these five patients was comparable to that observed preoperatively in patients with valvular heart disease.The results support the belief that, in contrast to artificial valve prostheses, heterograft valves behave similarly to human valves as regards haemolysis.     

Haemolysis complicating viral hepatitis in patients with glucose-6-phosphate dehydrogenase deficiency.

Out of 20 patients with viral hepatitis whose glucose-6-phosphate dehydrogenase (G-6-PD) levels were normal, 14 had clinical evidence of a mild to moderate degree of haemolysis but in all the patients studied the half life of chromium-51-labelled red cells was shortened. Out of 18 viral hepatitis patients deficient in G-6-PD 17 had clinical evidence of haemolysis, and in eight this was more severe than in the group with normal G-6-PD values. Massive intravascular haemolysis occurred in four, three of whom died. The massive haemolysis was attributed to the presence of additional drug-induced oxidative stress to the G-6-PD-deficient red cells.     

Late treatment of paracetamol poisoning with mercaptamine.

Forty patients who had taken overdoses of paracetamol were treated with mercaptamine. Twenty-three patients given mercaptamine within 10 hours of poisoning had normal liver function tests at follow-up, and one could not be traced. In 16 patients mecraptamine was begun more than 10 hours after ingestion of paracetamol ("late" mercaptamine). Eight of these patients developed severe liver damage, which in six was moderate or severe before mercaptamine administration. Acute renal failure occurred in two patients; in one other renal function was temporarily severely impaired. At follow-up two patients were not available, and one admitted moribund had died soon after admission. The remaining 13 all had normal liver function tests. It is concluded that late mercaptamine is not dangerous and may prevent further liver damage.     

Severe hypotension after first dose of enalapril in heart failure.

The new, long acting converting enzyme inhibitor enalapril was given to 26 patients with moderate to severe heart failure. In 23 cases the mean systolic blood pressure fell from 120 (SD 22) to 108 (25) mm Hg without adverse effects. Profound hypotension with severe bradycardia and sweating, however, occurred in three patients, most pronounced two to four hours after the first dose. The haemodynamic and biochemical changes in these patients were similar to those seen in patients with severe symptomatic hypotension after the first dose of the converting enzyme inhibitor captopril, except that with enalapril the changes occurred later and were longer lasting. Evidence of myocardial damage and reversible renal failure was seen in one patient, and acute reversible deterioration in renal function occurred in one other. In patients with heart failure converting enzyme inhibitors should be administered initially under strict medical supervision with appropriate facilities available for dealing with occasional profound hypotension.     

Inflammatory joint disease and human immunodeficiency virus infection

Nine men positive for antibody to human immunodeficiency virus (HIV) who developed peripheral, non-erosive arthritis were followed up. The clinical features were compatible with reactive arthritis but were atypical in several respects: the joint symptoms were generally severe, persistent, and unresponsive to non-steroidal anti-inflammatory drugs. The onset of arthritis was associated with various infections, none of which are known to be associated with the development of reactive arthritis. HLA typing was performed for three patients, all of whom were positive for HLA-B27. HIV was isolated from the synovial fluid of one patient. No patient had AIDS before developing arthritis, but four progressed to having AIDS after a mean of 7·5 months, and two died. Arthritis resolved in only one patient.The possibility of HIV infection should be considered in all patients with conditions suggesting reactive arthritis. Synovitis in patients with severe immunodeficiency has important pathogenetic implications.     

Treatment of severe side effects after vagotomy and gastroenterostomy by closure of gastroenterostomy without pyloroplasty.

We describe nine patients who had severe, persistent abdominal pain, vomiting, dumping, or diarrhoea several years after truncal vagotomy and gastroenterostomy had been performed for duodenal ulceration. Each patient was judged to have a bad clinical result (Visick grade 4). There was no evidence of recurrent ulceration in any of the patients, and in each the patency of the pyloric canal was confirmed radiologically or endoscopically. Each patient was treated by simply dismantling the gastroenterostomy without addition for a pyloroplasty. In one patient the surgeon suspected that a vagal trunk might have been left intact, and a revagotomy was performed by the "highly selective" technique. Postoperatively, none of the patients developed gastric retention. Symptomatic improvement occurred in eight patients, and four of them achieved perfect results (Visick grade 1). Side effects are common after vagotomy and gastroenterostomy, and are largely attributable to the presence of the gastroenterostomy stoma. Our results show that the symptoms may be alleviated by closing the gastroenterostomy, without precipitating gastric retention.     

Role of hepatic arterial embolisation in the carcinoid syndrome.

Eighteen patients with severe symptoms of the carcinoid syndrome were assessed for hepatic embolisation. Four were too ill, and one had mild symptoms; thus 13 received a periembolisation regimen of cyproheptadine, fenclonine, aprotinin, methylprednisolone, tobramycin, flucloxacillin, and metronidazole. Embolisation was not performed in one patient with an occluded portal vein and was unsatisfactory in two others, in one because she was moribund and in the other because the hepatic artery had been ligated. Dramatic improvement in symptoms occurred in the nine patients in whom embolisation was successfully carried out, with abolition of flushing, severe abdominal pain, and wheeze and reduction in diarrhoea from 10.5 (SD 7.6) to 1.6 (0.9) stools/day. Urinary excretion of 5-hydroxyindole acetic acid fell from 1048 (716) to 289 (184) mumol/24 h (200 (137) to 55 (35) mg/24 h). Complications included one death from septicaemia, a hepatic abscess requiring surgical drainage, abdominal pain in three patients, pleural effusion in two, and transient encephalopathy in one. Relief of symptoms lasted for one to 24 months, and second embolisation in two patients produced further remissions of four to six months. Five patients died, one to 40 months after embolisation, in four cases because of metastases or heart failure. Hepatic embolisation is the treatment of choice for symptoms of the carcinoid syndrome resistant to medical treatment.     

Flap failure after microvascular free-tissue transfer: the fate of a second attempt

In most cases, the loss of a free-tissue transfer is a disaster for both the patient and the surgeon. Seven patients received a second microvascular free-tissue transfer after loss of the first. The indications for free-tissue transfer included chronic osteomyelitis of the lower leg (four patients), acute traumatic defect of the leg (one patient), acute traumatic defect of the arm (one patient), and esophageal defect after surgical excision (one patient). In three patients, the interval between the first and second procedures was less than 2 weeks. The remaining four patients had their second free-tissue transfer performed 5 weeks to 21 months after the first. Six of the seven free flaps were successful. Two patients with venous obstruction occurring after the second free-tissue transfer were salvaged by reexploration. Partial loss of the flap was noted in one of these patients. It is concluded from this select group of patients that failure of a free-tissue transfer does not contraindicate a second microtissue transfer does not contraindicate a second microvascular free-tissue transfer.     

Use of Benzoctamine as Sedative in Patients with Respiratory Failure

Benzoctamine (Tacitin) was given by mouth as night sedation to patients admitted to hospital with respiratory failure. Fourteen patients had chronic obstructive bronchitis and six had acute severe asthma. One patient with asthma needed intravenous sedation with benzoctamine. No adverse effects were observed, and there was no significant change of forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), or Pco₂ in any patient after benzoctamine. Nevertheless, further clinical experience of the drug is required before its use can be safely recommended in respiratory failure.     

Inoperable aortic stenosis in the elderly: benefit from percutaneous transluminal valvuloplasty.

Eight patients with severe symptomatic calcific aortic stenosis were considered to be unsuitable for valve replacement. Four were admitted with pulmonary oedema and three in cardiogenic shock and one had angina at rest. With the use of echocardiographic and radiographic guidance percutaneous transluminal aortic valvuloplasty was carried out. Aortic gradients were reduced by an average of 40%. All four patients who presented with cardiac failure improved immediately and remained well six months later. The patient with angina was symptom free at nine months. Two of the three patients who presented in cardiogenic shock improved immediately and were well nine and three months later. The other patient died four hours after the procedure. Doppler echocardiographic studies showed a slight initial increase in aortic incompetence, but this did not worsen and valvar gradients remained improved three and six months later. Percutaneous valvuloplasty of the aortic valve is an effective therapeutic option in patients with severe calcific aortic stenosis who are unfit for surgery. Its role as an alternative to surgery has not been considered and should be investigated in a controlled clinical trial.     

Hospital Mortality in Acute Myocardial Infarction

All 757 patients with acute myocardial infarction admitted to the three public hospitals in Auckland during one year were studied. About 7% died from cardiac arrhythmia four days or more after the onset of infarction. These patients had severe infarcts with circulatory failure on or shortly after admission to hospital. Late death from arrhythmia in patients recovering from circulatory failure may in many cases be preventable with anti-arrhythmic drugs.     

Proximal gastric vagotomy versus long-term maintenance treatment with cimetidine for chronic duodenal ulcer: a prospective randomised trial.

Forty-four patients with chronic duodenal ulceration were allocated randomly to either long-term maintenance treatment with cimetidine or proximal gastric vagotomy. All were followed up both clinically and endoscopically for periods of one to four years. The rate of recurrence of ulcer during and after medical treatment was 54% while after surgery it was 10%. One patient developed severe allergic hepatitis while receiving maintenance treatment with cimetidine, and two others had to stop treatment because of possible drug reactions. Patients whose ulceration recurs while they are receiving treatment with cimetidine should be offered the possibility of operation.     

Successful Splenectomy for Hypersplenism in Wilson’s Disease: A Single Center Experience from China

Splenomegaly and pancytopenia are common in Wilson’s disease (WD) and splenectomy is one of the conventional treatments for splenomegaly and the associated pancytopenia. However, splenectomy remained controversial for hypersplenism in WD as it was reported that splenectomy leaded to serious emotional and neurological deterioration in WD patients with hypersplenism. In the current study, we present our experiences in 70 WD patients with hypersplenism who had undergone splenectomy, outlining the safety and efficacy of splenectomy in WD. The clinical database of 70 WD patients with hypersplenism who had undergone splenectomy in our hospital between 2009 and 2013 were reviewed and followed-up regularly. Before splenectomy, all the patients accepted a short period of anti-copper treatment with intravenous sodium 2, 3-dimercapto-1-propane sulfonate (DMPS). All the patients demonstrated a marked improvement in platelet and leucocyte counts after splenectomy. No severe postoperative complication was observed. In particular, none of the 37 patients with mixed neurologic and hepatic presentations experienced neurological deterioration after splenectomy, and none of the patients with only hepatic presentations newly developed neurological symptoms. During the one year follow-up period, no patient presented hepatic failure or hepatic encephalopathy, no hepatic patient newly developed neurological presentations, and only 3 patients with mixed neurologic and hepatic presentations suffered neurological deterioration and these 3 patients had poor compliance of anti-copper treatment. Quantative analysis of the neurological symptoms in the 37 patients using the Unified Wilson’s Disease Rating Scale (UWDRS) showed that the neurological symptoms were not changed in a short-term of one week after splenectomy but significantly improved in a long-term of one year after splenectomy. Additionally, compared to that before splenectomy, the esophageal gastric varices in most patients significantly improved one year after splenectomy. Thus, we may conclude that splenectomy is a safe and effective therapeutic measure for hypersplenism in WD patients who had been preoperatively treated with DMPS for powerful anti-copper therapy.     

Post-treatment haemolysis in severe imported malaria after intravenous artesunate: case report of three patients with hyperparasitaemia

ABSTRACT: Parenteral artesunate has been shown to be a superior treatment option compared to parenteral quinine in adults and children with severe malaria. Little evidence, however, is available on long-term safety. Recently, cases of late-onset haemolysis after parenteral treatment with artesunate have been reported in European travellers with imported Plasmodium falciparum malaria. Therefore, an extended follow-up of adult patients treated for severe imported malaria was started in August 2011 at the University Medical Center Hamburg-Eppendorf. Until January 2012, three patients with hyperparasitaemia (range: 14-21%) were included for analysis. In all three patients, delayed haemolysis was detected in the second week after the first dose of intravenous artesunate. Reticulocyte production index remained inadequately low in the 7 - 14 days following the first dose of artesunate despite rapid parasite clearance. Post-treatment haemolysis after parenteral artesunate may be of clinical relevance in particular in imported severe malaria characterized by high parasite levels. Extended followup of at least 30 days including controls of haematological parameters after artesunate treatment seems to be indicated. Further investigations are needed to assess frequency and pathophysiological background of this complication.     

Histological Reassessment of Three Kidneys Originally Described by Richard Bright in 1827-36

Portions of kidney from three patients with renal disease that were originally described by Richard Bright between 1827 and 1836 have been preserved in the Gordon Museum at Guy''s Hospital. Histological study has shown that two cases fall into the current diagnostic category of mesangiocapillary (membranoproliferative) glomerulonephritis. One of these patients had a five-year clinical history and died with chronic renal failure and uraemia. The other patient died after three to four months with a severe nephrotic syndrome. The third patient was a young woman with chronic “phthisis pulmonalis” and renal amyloidosis.     

Neurological complications of coronary artery bypass graft surgery: six month follow-up study.

As part of a major prospective study of the neurological complications of coronary artery bypass graft surgery patients were reviewed over six months to determine the clinical course and functional impact of early postoperative complications. One hundred and ninety one out of 312 (61%) patients had developed early postoperative disorders. At six months 165 of the 191 patients with early neurological complications were reviewed. Of the 165, 85 still had detectable neurological signs, but these were often minor and of little functional importance. Only 10 patients had neurological disability at six months, and this was major in only four patients, all of whom had suffered major perioperative stroke. No patient with non-disabling neurological complications in hospital became functionally impaired on returning home. Neurological disorders are not a major cause of failure to return to work by six months after coronary artery bypass surgery. Of 139 patients who were of working age and had not returned to work by six months, only four were prevented by neurological injury related to surgery. The long term prognosis for early neurological disorders after coronary artery bypass surgery is usually favourable, except in those patients who have sustained major perioperative stroke.     

Acute dacryocystitis: another clinical manifestation of sporotrichosis

Sporotrichosis associated with exposure to domestic cats is hyperendemic in Rio de Janeiro, Brazil. A review of the clinical records at our institute revealed four patients with clinical signs of dacryocystitis and a positive conjunctival culture for Sporothrix who were diagnosed with Sporothrix dacryocystitis. Three patients were children (< 13 years of age) and one patient was an adult. Two patients reported contact with a cat that had sporotrichosis. Dacryocystitis was associated with nodular, ulcerated lesions on the face of one patient and with granulomatous conjunctivitis in two patients; however, this condition manifested as an isolated disease in another patient. All of the patients were cured of the fungal infections, but three patients had chronic dacryocystitis and one patient developed a cutaneous fistula. Sporotrichosis is usually a benign disease, but may cause severe complications when the eye and the adnexa are affected. Physicians, especially ophthalmologists in endemic areas, should be aware of the ophthalmological manifestations and complications of sporotrichosis.     

Nd-YAG Laser Treatment of Tracheal Stenosis

We administered Nd-YAG laser treatments in four patients aged 56 to 68 years for severe tracheal stenosis, the tracheal diameters varying between 2.5 and 5 mm. These patients were all dyspneic at rest with talking or dressing and their peak flows ranged from 8% to 36% of predicted. They were not felt to be candidates for surgical excision. Immediate palliative relief was achieved in all patients and lasted two to four months after a single treatment in three patients. One patient died three weeks after laser treatment due to respiratory failure from underlying emphysema. There were no complications of laser therapy. Postlaser therapy the tracheal diameter in each patient was at least 9 mm and peak flow improved to between 25% and 76% of predicted. The results suggest that laser treatment may be beneficial in cases of severe tracheal stenosis.