Sensorineural hearing loss due to secondary syphilis.

We present a case of sudden sensorineural hearing loss occurring as a complication of secondary syphilis. Syphilis affecting the inner ear, or otosyphilis, is well described in historical literature, but has rarely been reported in recent times. However, following the resurgence of syphilis in the UK, unusual manifestations such as otosyphilis are likely to be seen increasingly commonly.

Successful treatment of AIDS-related cryptosporidial sclerosing cholangitis.

OBJECTIVE: Cryptosporidium is a well recognized cause of AIDS-related sclerosing cholangitis for which no efficacious therapy exists at present. We evaluated the efficiency of the combination of paromomycin and letrazuril in the treatment of this condition. CASE REPORT: We report a case of cryptosporidial cholangitis in a patient with AIDS who responded to treatment with intravenous paromomycin followed by oral letrazuril as maintenance therapy. CONCLUSION: The combination of paromomycin and letrazuril should be considered in the treatment of AIDS-related sclerosing cholangitis.

Tumour necrosis factor c2 microsatellite allele is associated with the rate of HIV disease progression.

BACKGROUND: The rate of immunological deterioration and progression to AIDS differs markedly between HIV-positive individuals, and may be influenced by cofactors, HIV phenotype and host T-cell response. Tumour necrosis factor (TNF)-alpha and lymphotoxin stimulate HIV replication and may induce apoptosis of HIV-infected and uninfected lymphocytes in vitro, thus accelerating disease progression and CD4 depletion. Variability in TNF production between individuals is to a degree genetically determined and may be predicted from polymorphisms of microsatellite regions surrounding the human TNF gene locus. METHODS: We examined TNf microsatellite polymorphisms in 24 HIV-positive patients with slower disease progression (CD4 count > 400 x 10(6)/l at > or = 6 years), 20 HIV-positive patients with faster progression (CD4 count < 200 x 10(6)/l within 5 years) and 109 healthy controls resident in north-west England. Typing was performed by polymerase chain reaction amplification of TNF a, b, c and d microsatellites and alleles were defined using fluorescence-based semi-automated microsatellite mapping techniques. RESULTS: No significant differences in TNF a, b and d allele frequencies were observed between faster and slower progressors, or with healthy controls. The frequency of the TNF c2 allele was significantly different between HIV-positive slower (60.9%) and faster (15%) progressors (P = 0.002) with an odds ratio of 0.1 (95% confidence interval, 0-0.6). TNF c2 was also less frequent in faster progressors than in healthy controls (45.9%, P = 0.006) with an odds ratio of 0.2 (95% confidence interval 0-0.8). CONCLUSIONS: This is the first report demonstrating a strong association between the TNF c2 allele and the rate of HIV progression. Although it is possible that this finding may have arisen as a result of linkage disequilibrium with other alleles within the major histocompatibility complex that exert a more powerful effect upon progression, evidence is mounting to suggest that both TNF-alpha and lymphotoxin are closely involved in HIV disease progression and CD4 depletion. Our results serve to highlight the potential importance of genetic polymorphism, particularly of the TNF locus, in influencing the progression of HIV infection.

Intracellular glutathione in the peripheral blood cells of HIV-infected patients: failure to show a deficiency.

OBJECTIVE: To determine whether HIV-infected patients have a deficiency of intracellular glutathione (GSH) in peripheral blood mononuclear cells (PBMC) and erythrocytes. DESIGN: Initial experiments determining the stability of intracellular GSH preceded the measurement of GSH levels in 33 HIV-positive patients and 40 control subjects within 1 h of isolation of their blood cells. In addition, the susceptibility of erythrocytes to dapsone hydroxylamine-induced methaemoglobinaemia was evaluated. METHODS: GSH levels were determined by an high-performance liquid chromatography method utilizing a fluorescent probe, monobromobimane. The bimane-GSH adduct formed in PBMC was also characterized by mass spectrometry. Methaemoglobin formation on exposure to dapsone hydroxylamine was determined spectrophotometrically. RESULTS: GSH levels remained stable for only 1 h after cell isolation, thereafter showing a decrease of 20 and 60% at 4 and 24H, respectively, There was no difference in the GSH levels in PBMC and erythrocytes of the HIV-positive patients compared with controls. The GSH levels were not related to the disease stage or to CD4+ cell counts. There was no difference in GSH levels in PBMC taken from trimethoprim-sulphamethoxazole-hypersensitive and non-hypersensitive patients. Methaemoglobinaemia on exposure of erythrocytes to dapsone hydroxylamine was concentration-dependent, but there was no significant difference between patients and controls. CONCLUSION: In contrast to previous studies, no deficiency of intracellular GSH in the PBMC and erythrocytes of HIV-infected patients was found. The discrepancy between studies may be methodological reflecting the instability of GSH, which requires prompt sample analysis.

Influenza-like episodes in HIV-positive patients: the role of viral and 'atypical' infections.

OBJECTIVES: To document viral and 'atypical' infections in HIV-positive patients and association with influenza-like symptoms. PATIENTS AND METHODS: Monthly culture of urine, faeces and throat swabs in 63 HIV-positive patients (30 asymptomatic and 33 with AIDS-related complex/AIDS) over 5-27 months (with 1125 patient-months of follow-up), with further sample collections during influenza-like episodes. Standard viral detection methods were used. Throat swabs were assessed for Chlamydia sp. by culture and immunoblotting, and for Mycoplasma pneumoniae by polymerase chain reaction. RESULTS: Viruses were detected in 15 (50%) and M. pneumoniae in nine (30%) out of 30 HIV-positive patients during an influenza-like illness. A close temporal relationship with symptoms was observed in 12 (40%) patients: cytomegalovirus in six (20%), M. pneumoniae in three (10%), herpes simplex virus in three (10%), and enterovirus in one (4%). Influenza-like symptoms were more frequent in asymptomatic HIV infection than in AIDS-related complex/AIDS patients (actuarial risk at 1 year, 63 versus 26%; P=0.002), particularly in those with CD4 cell counts >300 x 10(6)/l at enrolment (P=0.002). At least 44% (four out of nine) M. pneumoniae infections were asymptomatic and 78% (seven out of nine) were associated with prolonged excretion (2-17 months). Chlamydia sp. were not detected. CONCLUSIONS: Influenza-like symptoms were more likely to be reported by HIV-positive patients at early stages of disease, possibly as a result of differences in immune responses to viral infection. There was a close association in 40% of cases between the development of symptoms and detection of cytomegalovirus, herpes simplex virus, enterovirus and M. pneumoniae (a previously unrecognized association).

The effect of zidovudine dose on the formation of intracellular phosphorylated metabolites.

OBJECTIVES: Zidovudine (ZDV) requires intracellular phosphorylation to ZDV triphosphate (ZDV-TP) prior to the inhibition of HIV replication. The effect of ZDV dose on the formation of intracellular phosphorylated metabolites may help define the optimum daily dose of ZDV, which is still unknown. DESIGN AND METHODS: The plasma and intracellular phosphorylated metabolite concentrations of ZDV were determined over a 12 h period following oral administration of 100 and 300 mg ZDV to 10 HIV-seropositive patients at steady state during two dosing regimens (i.e., 100 mg three times daily and 300 mg twice daily). The intracellular ZDV phosphates, ZDV monophosphate (ZDV-MP), ZDV diphosphate (ZDV-DP) and ZDV-TP were measured in peripheral blood mononuclear cells using a combination of high-performance liquid chromatography and radioimmunoassay. RESULTS: There was a greater than threefold increase in maximum plasma concentration (Cmax) following 300 mg ZDV when compared with 100 mg ZDV (mean +/- SD, 2.59 +/- 0.52 versus 0.70 +/- 0.14 mumol/l). The area under the concentration time curve (AUC0-12 h) was also significantly increased (4.59 +/- 0.79 versus 1.42 +/- 0.51 mumol/l x h) following 300 mg ZDV dose. For total intracellular ZDV phosphate metabolites the AUC0-12 h was doubled (7.64 +/- 3.67 versus 3.71 +/- 1.83 pmol/10(6) cells x h) in patients taking 300 mg ZDV compared with 100 mg. The AUC0-12 h for ZDV-MP was significantly increased at the higher dose (6.47 +/- 3.14 versus 2.77 +/- 1.70 pmol/10(6) cells x h), whereas the active moiety ZDV-TP was variable and not significantly different (0.42 +/- 0.42 versus 0.61 +/- 0.81 pmol/10(6) cells x h) following 100 and 300 mg ZDV. CONCLUSIONS: Administration of 100 mg ZDV orally produces significantly less of the potentially toxic metabolite, ZDV-MP, and comparative, although variable, concentrations of the active metabolite ZDV-TP when compared with 300 mg ZDV orally. This finding supports clinical data indicating the efficacy of low-dose (300 mg daily) ZDV. The measurement of intracellular phosphorylated metabolites advances our understanding of the clinical pharmacology of ZDV.

Association analysis of drug metabolizing enzyme gene polymorphisms in HIV-positive patients with co-trimoxazole hypersensitivity.

The use of co-trimoxazole in HIV-positive patients has been associated with a high frequency (40-80%) of hypersensitivity reactions. This has been attributed to the bioactivation of the sulphonamide component, sulphamethoxazole (SMX), to its toxic hydroxylamine and nitroso metabolites. The aim of this study was to determine whether functionally significant polymorphisms in the genes coding for enzymes involved in SMX metabolism influence susceptibility to SMX hypersensitivity. HIV-positive patients with (n = 56) and without (n = 89) SMX hypersensitivity were genotyped for allelic variants in CYP2C9, GSTM1, GSTT1, GSTP1 and NAT2 using polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymorphism analysis. The CYP2C9*2/*3 genotype and CYP2C9*3 allele frequencies were nine- and 2.5-fold higher in the hypersensitive group compared to non-sensitive patients, respectively, although they were not statistically significant when corrected for multiple testing. There were no differences in the frequencies of the GSTM1 and GSTT1 null genotypes, and the slow acetylator genotype, between hypersensitive and non-sensitive patients, while GSTP1 frequency was lower (although non-significant) in the hypersensitive group [21% versus 32%, odds ratio (OR) = 0.5, Pc = 0.24]. Comparison of the genotype frequencies in HIV-positive and -negative patients showed that the NAT2 slow acetylator genotype frequency in the HIV-positive patients (74%) was significantly (Pc = 0.0003, OR = 2.3) higher than in control subjects (56%). Our results show that genetic polymorphisms in drug metabolizing enzymes are unlikely to be major predisposing factors in determining individual susceptibility to co-trimoxazole hypersensitivity in HIV-positive patients.

Complications and patient satisfaction following expander/implant breast reconstruction with and without radiotherapy.

PURPOSE: To compare the rates of complications and patient satisfaction among breast cancer patients treated with mastectomy and tissue expander/implant reconstruction with and without radiotherapy. METHODS AND MATERIALS: As part of the Michigan Breast Reconstruction Outcome Study (MBROS), breast cancer patients undergoing mastectomy with reconstruction were prospectively evaluated with respect to complications, general patient satisfaction with reconstruction, and esthetic satisfaction. Included in this study was a cohort of women who underwent breast reconstruction using an expander/implant (E/I). A subset of these patients also received radiotherapy (RT). At 1 and 2 years postoperatively, a survey was administered which included 7 items assessing both general satisfaction with their reconstruction and esthetic satisfaction. Complication data were also obtained at the same time points using hospital chart review. Radiotherapy patients identified in the University of Michigan Radiation Oncology database that underwent expander/implant reconstruction but not enrolled in the MBROS study were also added to the analysis. RESULTS: Eighty-one patients underwent mastectomy and E/I reconstruction. Nineteen patients received RT and 62 underwent reconstruction without RT. The median dose delivered to the reconstructed breast/chest wall, including boost, was 60.4 Gy (range, 50.0-66.0 Gy) in 1.8- to 2.0-Gy fractions. With a median follow-up of 31 months from the date of surgery, complications occurred in 68% (13/19) of the RT patients compared to 31% (19/62) in the no RT group (p = 0.006). Twelve of 81 patients (15%) had a breast reconstruction failure. Reconstruction failure was significantly associated with experiencing a complication (p = 0.0001) and the use of radiotherapy (p = 0.005). The observed reconstruction failure rates were 37% (7/19) and 8% (5/62) for patients treated with and without radiotherapy, respectively. Tamoxifen was associated with a borderline risk of complications (p = 0.07) and a significant risk of reconstruction failure (p = 0.01). Sixty-six patients of the study group completed the satisfaction survey; 15 patients did not. To offset potential bias for patients not completing the survey, we analyzed satisfaction data assuming "dissatisfaction" scores for surveys not completed. In the analysis of patients with unilateral E/I placement, reconstruction failure was significantly associated with a lower general satisfaction (p = 0.03). Ten percent of patients experiencing a reconstruction failure were generally satisfied compared to 23% who completed E/I reconstruction. In addition, tamoxifen use was associated with a significantly decreased esthetic satisfaction (p = 0.03). Radiotherapy was not associated with significantly decreased general or esthetic satisfaction. CONCLUSION: Irradiated patients had a higher rate of expander/implant reconstruction failure and complications than nonirradiated patients. Despite these differences, our pilot data suggest that both general satisfaction and patient esthetic satisfaction were not significantly different following radiotherapy compared to patients who did not receive RT. Although statistical power was limited in the present study and larger patient numbers are needed to validate these results, this study suggests comparable patient assessment of cosmetic outcome with or without radiotherapy in women who successfully complete expander/implant reconstruction.

Plasma cysteine deficiency and decreased reduction of nitrososulfamethoxazole with HIV infection.

The aim of these studies was to determine whether HIV-infected patients have a plasma thiol deficiency and whether this is associated with decreased detoxification of the toxic metabolites of sulfamethoxazole. Reduced, oxidized, protein-bound, and total thiol levels were measured in 33 HIV-positive patients and 33 control subjects by an HPLC method utilizing the fluorescent probe bromobimane. The reduction of sulfamethoxazole hydroxylamine and nitrososulfamethoxazole by plasma and the plasma redox balance in the presence of nitrososulphamethoxazole were also determined by HPLC. Reduced plasma cysteine was significantly (p<0.0001) lower in HIV-positive patients (13.0+/-3.0 microM) when compared with control subjects (16.9+/-3.0 microM). Although there was no difference in oxidized, protein-bound, and total cysteine, the thiol/disulfide ratios were lower in HIV-positive patients. Reduced homocysteine was elevated in patients. Plasma from HIV-positive patients was less able to detoxify nitrososulfamethoxazole than control plasma. These findings show that the disturbance in redox balance in HIV-positive patients may alter metabolic detoxification capacity, and thereby predispose to sulfamethoxazole hypersensitivity.

Leucocyte esterase-nitrite screening method for pyuria and bacteriuria.

The value of the one minute leucocyte esterase-nitrite chemical strips as a screening procedure for detecting appreciable levels of pyuria and bacteriuria was assessed by comparison with microscopy and culture results. The likelihood that a negative leucocyte esterase result indicated less than 10 white cells/cu mm by microscopy (the negative predictive value), was 90.1% and that a negative nitrite result indicated less than 10(5) organisms/ml was 91.3%. There were many false positive results with both tests, however, and the overall predictive value of a positive leucocyte esterase or nitrite test, or both, was low. The leucocyte esterase-nitrite strip was neither sufficiently sensitive nor specific enough to be used as a cost effective method for screening urines in the laboratory.

Serodiagnosis of pericardial tuberculosis.

The AIDS epidemic has led to the resurgence of tuberculosis. Extrapulmonary manifestations may appear in over half of the patients who are dually infected. This has resulted in a rising incidence of tuberculous pericarditis in several parts of Africa such as Tanzania. We tested a solid-phase antibody competition sandwich ELISA (SACT-SE) as a potential means of diagnosing tuberculous pericarditis. Fifty-one African patients with clinically diagnosed tuberculous pericardial effusion (of whom 25 had confirmation by pericardial fluid culture) were tested using a monoclonal antibody (CDC/WHO ref. no. IT39) which was raised against a specific epitope on the Mycobacterium tuberculosis 30 kDa antigen. All but one patient had negative sputum microscopy for acid-fast bacilli. A sensitivity of 61% (at 96% specificity) was achieved. Sera from 25 African patients with smear-positive tuberculosis were also examined; of which 20 tested positive (sensitivity 80%). This is the largest study to date on the potential application of serology in diagnosing pericardial tuberculosis.

Immediate transverse rectus abdominis musculocutaneous flap reconstruction after mastectomy.

BACKGROUND: This study examines the early and long-term outcomes of immediate transverse rectus abdominis musculocutaneous (TRAM) reconstruction of the breast after mastectomy. STUDY DESIGN: The records of all patients undergoing mastectomy and immediate TRAM breast reconstruction between December 1989 and October 1993 were reviewed retrospectively using hospital and breast care center databases. RESULTS: Fifty-three patients underwent a total of 73 immediate TRAM breast reconstructions. Reconstruction was successfully completed in all patients, using 46 pedicle flaps and 27 free tissue transfers. There were no flap losses or cardiopulmonary complications. Overall, the complication rate was 26 percent (29 percent for pedicle TRAM and 22 percent for free TRAM flaps). The median follow-up period among the 53 patients was 22.6 months (range of three to 48 months). All patients employed preoperatively resumed their occupations postoperatively. CONCLUSIONS: Our experience indicates that immediate TRAM breast reconstruction is a safe and viable option for patients seeking reconstruction at the time of mastectomy.

Screening for enteropathogenic Escherichia coli.

In an attempt to identify the prevalence of enteropathogenic Escherichia coli (EPEC) carriage and to minimize the chances of admitting a baby to the neonatal wards with unsuspected EPEC infection, 27,174 maternity patients admitted in labour and 4049 neonates admitted to the Special Care Baby Unit (SCBU) were screened for intestinal carriage of common EPEC serotypes. Two hundred and sixty-five (1%) maternity patients were positive, of whom 8 (3%) had diarrhoea. Of the babies born to these mothers, 10 (3.8%) were infected with EPEC and in each the serotype was the same as the mother's. Nine neonates (0.2%) admitted to the SCBU were also found to be infected with EPEC. Seven of the 19 babies (37%) had diarrhoea. Symptomatic mothers or babies were nursed in isolation. During the 8 year period under study no incidents of cross-infection with EPEC occurred.

Salmonella screening of pregnant women.

Over a 9-year period all maternity patients were screened by rectal swab for salmonella excretion at the time of delivery. 30,471 mothers were screened and 60 (0.2%) yielded salmonellas, 43 (72%) of whom were symptomless excretors. Seven of the 60 babies (12%) excreted salmonellas, all of which were the same organism as in the mothers. Five had uncomplicated gastroenteritis in the neonatal period, but no mother or child suffered invasive disease and no incidents of hospital cross-infection occurred. These results show that screening is unjustified unless there are problems of cross-infection.

Quantitative bacteriology of peripheral venous cannulae in neonates.

In a study of 50 peripheral venous cannulae removed from neonates in the special care baby unit, quantitative and qualitative techniques for cannula culture were compared and the results correlated with detailed clinical information. High-density colonization was demonstrated on the external and internal surfaces of nine, and on the external surface alone of four, cannula tips. Internal surface colonization was always associated with heavy external surface growth. In predicting high-density colonization by quantitative methods, qualitative culture in broth was 100% sensitive and 89% specific. There was a significant association between high-density colonization of the cannula tip and hub colonization, surrounding skin colonization, longer duration of cannula insertion, and slower average infusion rate. Similar organisms were isolated more frequently from the cannula tip and the hub than from the cannula tip and surrounding skin. These findings indicate that peripheral venous cannulae are a potential source of infection in neonates, that there is no advantage of techniques that identify internal surface colonization, and that most cannula tip infections have their origin in a colonized hub.

Severe hyponatraemia in malaria.

We report a case of severe hyponatraemia and hypoglycaemia in a patient with complicated falciparum malaria. The use of large volumes of intravenous dextrose as a diluent for quinine may lead to fluid overload and exacerbate hyponatraemia.

Outcome of varicella pneumonitis in immunocompetent adults requiring treatment in a high dependency unit.

OBJECTIVES: The incidence of varicella infection is increasing in adults, where primary pneumonitis is the main complication. Little information exists concerning treatment of those patients who require admission to a high dependency unit (HDU) facility. A study was performed to examine the risk factors for developing varicella pneumonitis (VP), to document disease progression and assess prognosis for patients with VP requiring HDU admission. METHODS: A 10-year retrospective casenote review of patients admitted to the Regional Infectious Diseases Unit HDU. Varicella pneumonitis (VP) was defined as diffuse nodular shadowing on a chest X-ray (CXR) of a patient with a classical chickenpox rash. Severe pneumonitis was defined as an hypoxaemia index (pO2 in mmHG/FiO2) of less than 150 at any time during hospital stay. All patients were treated with intravenous acyclovir at a dose of 10 mg/kg. RESULTS: A total of 33 patients were admitted to the HDU with VP over the study period, 30 were included in the study. Annual admission rates remained constant. Most patients (76.7%) had at least one recognised risk factor for severe VP: smoking 18/30, pregnancy 9/30, chronic lung disease 7/30. Twelve (40%) patients had severe VP, eight (26.7%) required assisted ventilation. The presence of greater than one risk factor (p < 0.02) was associated with progression to severe VP. There was one death: a 63-year-old man with a long history of chronic airflow limitation whose treatment had included domicillary long-term oxygen therapy. Nine (30%) patients developed secondary bacterial pneumonia; all recovered with appropriate antibiotic treatment. The period of stay in HDU for the majority of patients was short (mean 4.5 days). CONCLUSIONS: The prognosis for severe adult VP with current available treatment is good. The only predictor on admission for severe VP is the presence of more than one recognised risk factor for developing VP.

Severe community acquired pneumonia associated with a desquamating rash due to group A beta-haemolytic streptococcus.

In recent years frequent and severe infections due to group A beta-haemolytic streptococci have been recognised with increasing frequency. Group A streptococcal pneumonia remains a rare disease occurring sporadically in contrast to epidemics in the past. The association between group A streptococcal pneumonia and a desquamating skin rash typical of scarlet fever has rarely been reported.

Valvular tuberculous endocarditis: a case report and review of the literature.

Tuberculous valvular endocarditis is exceptionally rare. It is usually manifest in the context of miliary tuberculosis, and in all but one case the diagnoses have been made at necropsy. Because of its rarity there is still uncertainty as to whether true tuberculous endocarditis exists as a clinical entity. This paper describes a case of miliary tuberculosis with aortic valvulitis that resolved on antituberculous therapy.

Does isolation of patients with infections induce mental illness?

Forty-one patients admitted into single-bedded isolation cubicles in an infectious diseases unit were assessed for evidence of mental disturbance. By use of the Crown-Crisp Experimental Index as a measure of mental state, the scores for somatic anxiety, free floating anxiety, and the total score were found to be significantly raised on admission, falling towards those found in a control general practice population by the time of discharge from hospital. Higher scores were associated with a past history of mental illness. There was, however, no statistical correlation between the psychological indices and consumption of alcohol, smoking, or patient's sex. Clinically apparent behavioural disturbance, mainly anxiety and agitation, was seen in 12 patients. Overall, patients expressed a preference for single rooms and did not find the isolation rituals disconcerting. The findings indicate that anxiety in patients with acute infections is more related to their illness and referral to hospital than to their imposed isolation. Only those patients with a past psychiatric history are likely to benefit from transfer to an open ward during convalescence.