Course, management and outcome of oral-anticoagulant-related intracranial haemorrhages.

The aim of this study was to compare the clinical course and radiological features of oral anticoagulant (OAC)-related intracranial haemorrhages with those of haemorrhages unrelated to OAC use admitted over the last six years to a tertiary care centre in the North of Scotland. We furthermore wished to determine the measures taken for reversal of OAC therapy and the resulting short-term outcome. Sixty-eight patients had been treated with OACs at the time of intracranial haemorrhage (32% subdural, 62% intracerebral). Patients admitted with OAC-related and unrelated haemorrhages did not differ significantly in any of the clinical features considered. On CT scan, there was no significant difference according to OAC use in the mean size of subdural (depth 15 +/- 5 vs. 18 +/- 8 mm, p = 0.36), or intracerebral haematomas (max. diameter 40 +/- 21 vs. 41 +/- 20 mm, p = 0.73). No reversal measures were taken in 38% of OAC-treated patients. In-hospital mortality was significantly higher for OAC-related haemorrhages compared to unrelated haemorrhages (38% vs. 18%, p = 0.001). To further elucidate the effects of anticoagulant reversal on the outcome of OAC-related intracranial haemorrhages, a large-scale prospective study is warranted.

Nitric oxide synthesis in patients with infective gastroenteritis.

BACKGROUND: There is evidence that endogenous nitrate synthesis is notably increased in patients with infective gastroenteritis. AIMS: To determine whether this is due to nitric oxide (NO) production via the L-arginine/NO pathway. METHODS: Seven male patients with community acquired bacterial gastroenteritis and 15 healthy male volunteers participated in this study. All patients had stool culture positive infective gastroenteritis. A bolus of 200 mg L-[(15)N](2)-arginine was administered intravenously after an overnight fast. Urine was collected for the next 36 hours. Urinary [(15)N:(14)N]nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer. RESULTS: Mean 36 hour total urinary nitrate excretion in the gastroenteritis group was 5157 (577) micromol compared with 2594 (234) micromol in the control group (p<0.001). Thirty six hour urinary [(15)N]nitrate excretion was considerably higher in the gastroenteritis group compared with the control group (13782 (1665) versus 1698 (98) etamol; p<0.001). These values represent 1.129 (0.139)% and 0.138 (0.007)% of [(15)N]nitrogen administered (p<0.001), respectively. Corrected 36 hour urinary [(15)N]nitrate excretion for urinary creatinine was also significantly higher in the patient compared with the control group (1934 (221) versus 303 (35) etamol/mmol; p<0.001). CONCLUSION: Results show notably enhanced nitrate synthesis due to increased activity of the L-arginine/NO pathway in patients with infective gastroenteritis.

Helicobacter pylori is killed by nitrite under acidic conditions.

BACKGROUND: Due to the expression of urease, Helicobacter pylori is able to establish itself in the human stomach under acidic conditions. A novel host defence mechanism was recently proposed, suggesting that the formation of salivary nitrite in symbiosis with facultative anaerobic bacteria in the oropharynx, is aimed at enhancing the antimicrobial activity of gastric juice. AIMS: To investigate whether the addition of nitrite in physiological concentrations influences the resistance of H pylori to acid. METHODS: H pylori cultured from fresh gastric Biopsy specimens was exposed for 30 minutes to normal saline and to HCl/KCl buffer (0.2M) at pH 2 with urea (5 mM) added. The influence of potassium nitrite (50-1000 mumol/l) on bacterial survival was determined. RESULTS: Addition of nitrite (1 mM) to acidic solutions (pH 2) resulted in complete kill of H pylori within 30 minutes exposure time whereas acid alone allowed the organism to survive (p < 0.001). The antimicrobial effect of nitrite at pH 2 against H pylori was dose dependent and complete kill of organisms occurred at concentrations > or = 500 mumol/l. CONCLUSION: Acidified nitrite has anti-bacterial activity against H pylori. This should prompt further research into the effect of salivary nitrite on the survival of H pylori in the human stomach.

Necrotizing sarcoid granulomatosis with extrapulmonary involvement.

Pulmonary lesions, with sarcoid-like granulomas exhibiting noncaseous necrosis, with associated granulomatous arteritis fulfil the diagnostic criteria of necrotizing sarcoid granulomatosis (NSG). We report the case of a woman who presented with recurrent headaches, transient right hemipareses and left-sided ophthalmoplegia. An excised left retro-orbital lesion demonstrated sarcoid like changes, and the illness responded to steroid therapy. Twelve years later, the patient developed a tumour in the right lung. The resected specimen showed the histological hallmarks of NSG, and careful review of the retro-orbital lesion, removed 12 years previously, revealed similar histology. Extrapulmonary involvement in NSG is rare and has been histologically proven on only one previous occasion. The presentation of necrotizing sarcoid granulomatosis in two different systems 12 years apart is unusual and was considered worth reporting.

Parenteral ganciclovir treatment of acute CMV infection in the immunocompetent host.

The treatment with ganciclovir of two non-compromised patients who required hospitalisation with acute cytomegalovirus (CMV) infection is described. Ganciclovir has rarely been used in such circumstances but, in four previously reported patients and in the patients described here, a rapid response to therapy was seen. In contrast to previous reports, relatively short courses of treatment (3-5 days) were given to our patients. The drug was well tolerated in each case and may have a role to play in the treatment of severe acute CMV infection in the normal host.

Plasma nitrate concentration in infective gastroenteritis and inflammatory bowel disease.

BACKGROUND: In subjects on a low nitrate diet, plasma nitrate concentration and urinary nitrate excretion are thought to reflect endogenous nitric oxide (NO) production, and have been reported to increase during infective and inflammatory bowel disease. AIMS: To compare the extent of NO production in patients with infective versus non-infective forms of bowel dysfunction. SUBJECTS: Four groups: 20 healthy, volunteer clerical and laboratory staff, 12 patients with irritable bowel syndrome, 19 patients with inflammatory bowel disease, and 20 patients with infective gastroenteritis. METHODS: The plasma nitrate concentration was determined with a copper coated cadmium column and spectrophotometry. Mean and median plasma nitrate concentrations were calculated and compared within the four groups. Mann-Whitney distribution free rank testing was used to compare the median values. RESULTS: Median plasma nitrate concentrations in the four groups were: controls 32.7 mumol/l; irritable bowel syndrome 35.5 mumol/l; inflammatory bowel disease 35.1 mumol/l; and gastroenteritis 117.9 mumol/l (p < 0.001 gastroenteritis v all other groups). CONCLUSIONS: Plasma nitrate concentration could serve as a discriminant between infective and inflammatory or functional bowel disease in patients presenting with diarrhoea. It is not clear why there is considerable difference in endogenous nitrate synthesis in these two conditions, which are both characterised by severe gut inflammation.

Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defense.

Dietary intake of nitrate generates salivary nitrite, which is acidified in the stomach, leading to a number of reactive intermediates of nitrogen, among which are the potentially carcinogenic N-nitrosamines. Acidified nitrite, however, also has antimicrobial activity which coincides with the formation of nitric oxide. The present study examines the antimicrobial effect in vitro of acidified nitrite on Salmonella enteritidis, Salmonella typhimurium, Yersinia enterocolitica, Shigella sonnei, and Escherichia coli O157. First-order regression plots showed a linear inverse relationship of log-transformed proton and nitrite concentrations with MICs and MBCs after 30 min, 2 h, and 24 h of exposure (P < 0.001 for all antibacterial activities). Susceptibility to the acidified nitrate solutions ranked as follows: Y. enterocolitica > S. enteritidis > S. typhimurium = Shigella sonnei > E. coli O157 (P < 0.05). Addition of SCN-, but not that of CI-, increased the antibacterial activity (paired t testing, P < 0.001). Generation of salivary nitrite from dietary nitrate may provide significant protection against gut pathogens in humans.

Community-acquired toxigenic Clostridium difficile diarrhoea in the normoxaemic elderly who have received no antimicrobials: soft evidence for ischaemic colitis?

We report three examples of community-acquired toxigenic Clostridium difficile diarrhoea in elderly patients who had neither received antimicrobial therapy nor been institutionalised. These cases stimulated interest in the non-antimicrobial changes which might predispose the host to C. difficile-related disease and raised the spectre of bowel ischaemia as a possible aetiological factor.

Phenoxymethyl penicillin versus co-amoxiclav in the treatment of acute streptococcal pharyngitis, and the role of beta-lactamase activity in saliva.

One hundred and sixty-five consecutive patients ( > 2 years of age) with acute group A streptococcal (GAS) pharyngitis randomly received co-amoxyclav (79 patients) or phenoxymethyl penicillin (86 patients). beta-Lactamase activity in saliva was determined for each patient. At follow up after seven days, tonsillar cultures from seven patients (9.6%) in the penicillin V group grew group A streptococcus; three of these patients had tonsillitis clinically. In the co-amoxiclav group these figures were three (3.8%) and two respectively (P > 0.05). Within the 12 month follow up period, there were four clinical recurrences (6.1%) in the penicillin V group and seven (9.3%) in the co-amoxiclav group (P > 0.1). beta-Lactamase activity in the saliva was demonstrated in 29 patients (19.2%). Fourteen (74%) of 19 bacteriological failures or clinical recurrences had beta-lactamase activity, versus 15 (12%) of 129 successfully treated patients (P < 0.001). There is no evidence that oral co-amoxiclav is better than oral penicillin V for the first treatment of acute GAS pharyngitis, but bacteriological failure and clinical recurrence are strongly associated with the presence of beta-lactamase activity in commensal flora.

Protein binding and serum bactericidal activities of vancomycin and teicoplanin.

In a randomized crossover study, the protein binding and serum bactericidal activities (SBAs) of vancomycin and teicoplanin against Staphylococcus aureus and Streptococcus pyogenes were investigated in six healthy volunteers. Total concentrations in serum 1 h postadministration of vancomycin and teicoplanin were 25.5 +/- 2.7 and 10.8 +/- 8.9 mg/liter, respectively; mean free concentrations were 14.6 +/- 2.0 and 0.6 +/- 0.9 mg/liter, respectively. Protein binding for vancomycin was 36.9% +/- 2.87%, and that for teicoplanin was 97.4% +/- 2.6%. SBA determined in pooled human serum at 1 h against S. aureus ranged from 1:8 to 1:32 for both vancomycin and teicoplanin. Against S. pyogenes SBA at 1 h ranged from 1:16 to 1:128 for vancomycin and 1:256 to 1:2,048 for teicoplanin. In vitro kill curve studies showed that vancomycin is slowly bactericidal and that teicoplanin is bacteriostatic. Despite having less in vitro cidal activity against the study isolates and having low or unrecordable levels of free drug in serum, teicoplanin demonstrated a similar or better SBA than vancomycin. SBA was more closely related to the total drug level (r = 0.77 for S. aureus and r = 0.79 for S. pyogenes) than the free level of teicoplanin (r = 0.59 for S. aureus and r = 0.56 for S. pyogenes). The high level of protein binding of teicoplanin did not seem to impair its antibacterial activity as measured by its SBA.

Plasma nitrate concentration and urinary nitrate excretion in patients with gastroenteritis.

The concentration of nitrate (the stable oxidation product of nitric oxide) in plasma and its excretion in urine was measured in 20 patients with a diagnosis of gastroenteritis. On day 1 of the illness plasma nitrate concentration was significantly elevated compared with a healthy control population (92.7 +/- 17.0 mumol/l vs. 33.1 +/- 1.6 mumol/l; P < 0.001) and continued to be elevated on days 2 and 3. Urinary nitrate excretion was also elevated. The plasma nitrate concentration correlated with disease severity as assessed by stool frequency and plasma urea concentration. Plasma nitrate concentration may be a sensitive and clinically useful indicator of severity of gastroenteritis.

The high vaginal swab in general practice: clinical correlates of possible pathogens.

Clinical features, diagnosis and treatment of 286 women whose high vaginal swabs (HVS) submitted by their general practitioners showed pure, heavy growth of Staphylococcus aureus, beta haemolytic streptococci groups A, C or G, Streptococcus milleri, Streptococcus pneumoniae or Haemophilus influenzae were analysed. Women with group A, C and G streptococci frequently had clinical vulvovaginitis and although the numbers were too small for statistical confirmation, S. pneumoniae and H. influenzae appeared to cause clinical disease as well. The association of S. aureus or S. milleri with clinical vulvovaginitis was much less convincing. It seems relevant for laboratories to report sensitivities for group A, C and G streptococci. Further research is needed to determine the pathogenicity of S. pneumoniae and H. influenzae.

Ecstasy induced hepatitis mimicking viral hepatitis.

Three cases of jaundice after ingestion of 3,4-methylenedioxymetamphetamine (MDMA), known as 'ecstasy', are reported and the complications associated with the misuse of this drug, which was initially misrepresented as 'safer than alcohol' are described. Ingestion of 'ecstasy' should be considered when investigating unexplained jaundice in younger patients.

Corynebacterium afermentans subsp. lipophilum: multiple abscess formation in brain and liver.

Corynebacterium afermentans, a species recently identified, has previously been isolated from human blood cultures. We report the case of a previously healthy 39-year-old man who developed a brain abscess and a liver abscess due to Corynebacterium afermentans subsp. lipophilum. The liver abscess penetrated through the diaphragm to cause pleural effusion and periostitis of the ribs. We believe this is the first reported case of disseminated infection with abscess formation due to this organism.

Necrobacillosis (Lemmiere's syndrome): a rare cause of necrotizing pneumonia.

The cases of four young and previously healthy patients with necrobacillosis are reported. All four patients presented with acute pharyngotonsillitis and pulmonary infiltrates due to metastatic abscesses, and had neutrophil leucocytosis and hypoalbuminaemia. Blood cultures grew Fusobacterium necrophorum and each patient responded to metronidazole.

An analysis of 900 consecutive admissions to a regional infection unit.

A total of 900 consecutive admissions to the Regional Infection Unit at the City Hospital Aberdeen in 1991 have been analysed and the results compared with a similar study during 1980 and 1981. The annual number of admissions increased from 605 to 900, of which 72% in 1991 had proven infections compared with 60% a decade earlier. More patients were admitted with gastroenteritis, tonsillitis and soft tissue infection in 1991 and fewer with non-infectious jaundice. HIV-related conditions contributed 4% of the admissions and 29% of the mortality. Brucellosis disappeared as a reason for requesting hospital admission in North East Scotland.

Air crescent sign and fatal haemoptysis in pulmonary mucormycosis.

A case of invasive pulmonary mucormycosis complicated by fatal, massive haemoptysis in a patient with acute myeloid leukaemia is reported. This patient represents the twelfth reported case of fatal haemoptysis due to mucormycosis. The other 11 cases are reviewed and the aetiology of cavity formation and massive haemoptysis is discussed. The development of the air crescent sign on chest radiograph is an important clinical indicator of potentially fatal haemoptysis and should lead to appropriate antifungal and surgical therapy.