Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.     

Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions

Autosomal dominant cerebellar ataxia with progressive macular degeneration is caused by a CAG/glutamine repeat expansion in the SCA7 gene/protein. Neuronal intranuclear inclusions were detected in the brain of an early onset SCA7 case with the 1C2 antibody directed against an expanded polyglutamine domain. Nuclear inclusions were most frequent in the inferior olivary complex, a site of severe neuronal loss in SCA7. They were also observed in other brain regions, including the cerebral cortex, not considered to be affected in the disease. Using confocal microscopy we showed that some inclusions were ubiquitinated, but to varying degrees, ranging from <1% in the cerebral cortex to 60% in the inferior olive. In addition, we also observed cytoplasmic staining using the 1C2 antibody, particularly in the supramarginal gyrus, the hippocampus, the thalamus, the lateral geniculate body and the pontine nuclei. These data confirm that the presence of intranuclear inclusions in neurons is a common characteristic of disorders caused by CAG/polyglutamine expansions, but unlike what has been reported for Huntington's disease, SCA1 and SCA3/MJD, in SCA7 the inclusions were not restricted to the sites of severe neuronal loss.      

Peripelvic abscesses: a diagnostic dilemma

Acute hematogenous peripelvic infections are common in tropical climates. However, in more temperate regions, this is a rare and often overlooked diagnosis. Because of the subtle and subacute nature of the symptoms, the diagnosis is often delayed. We report our experience with nine children treated for a hematogenous peripelvic infection. The hospital and clinic charts were reviewed of nine consecutive patients with the diagnosis of a peripelvic abscess. Patients ranged in age from 2 to 13 years. Symptoms were present from 5 to 20 days. The most consistent symptom was a hip-flexion pseudocontracture (eight patients). The initial diagnosis was correct in only three patients. Computed tomography (CT) scan was diagnostic in all nine patients, providing diagnosis and localization. Seven of the nine patients underwent irrigation and debridement followed by a variable course of intravenous (i.v.) and oral antibiotics. All seven had rapid resolution of their symptoms. Two patients were treated with i.v. antibiotics alone, one of whom had a recurrence of symptoms. All nine patients had microbiologic confirmation of the infecting organisms [seven at surgery, one from blood cultures, one from sacroiliac (SI) joint aspiration]. Eight of the nine were infected by Staphylococcus aureus and one by group A Streptococcus. All had complete resolution of their symptoms at follow-up. Although acute retrofascial abscesses are rare in temperate climates, they should be considered in the differential diagnosis in the child with lower abdominal or hip pain. CT scan was the most helpful diagnostic test in these patients. Surgical drainage resulted in the most consistent results in this small series of patients.     

Thyroid dysfunction after mantle irradiation of Hodgkin's disease patients

Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated.     

CT-Cephalometry—A study in Indian population

Determination of obstructive site in obstructive sleep apnoea (OSA) is of paramount importance is planning the management. Cephalometric evaluation of lateral X-rays when combined with clinical assessment and fibreoptic examination of the airway helps in locating the site of obstruction. The usual technique of cephalometry has been modified so as to give a better delineation of the soft tissues. Holding a 2mm card board in the mouth and using barium paste helped in more accurate calculations. Using our technique, various parameters have been quantified and a number of controls were studied and normal range derived. Further improvement in cephalometry has been done by using C.T. cephlometry topogram technique. A topogram is a scan done on a running table top cranio-caudally. Using the topogram technique 38 OSA patients were evaluated for all the parameters. The technique, its advantages over traditional cephalometry and the values obtained in the study are discussed in this paper.     

TMD before and after correction of dentofacial deformities by orthodontic and orthognathic treatment

The aims of the study were to investigate the alteration of temporomandibular disorders (TMD) after correction of dentofacial deformities by orthodontic treatment in conjunction with orthognathic surgery; and to compare the frequency of TMD in patients with dentofacial deformities with an age and gender matched control group. TMD were evaluated in 121 consecutive patients (treatment group), referred for orthognathic surgery, by a questionnaire and a clinical examination. 18 months after treatment, 81% of the patients completed a follow-up examination. The control group comprised 56 age and gender matched subjects, of whom 68% presented for follow-up examination. TMD were diagnosed according to research diagnostic criteria for TMD. At baseline examination, the treatment group had a higher frequency of myofascial pain (P = .035) and arthralgia (P = .040) than the control group. At follow-up, the frequencies of myofascial pain, arthralgia and disc displacement had decreased in the treatment group (P = .050, P = .004, P = .041, respectively). The frequency of TMD was comparable in the two groups at follow-up. Patients with dentofacial deformities, corrected by orthodontic treatment in conjunction with orthognathic surgery, seem to have a positive treatment outcome in respect of TMD pain.     

Independent predictors of isolated clinic ('white-coat') hypertension

BACKGROUND: Hypertension guidelines recommend 24 h ambulatory blood pressure (ABP) monitoring in hypertensive subjects with suspected isolated clinic hypertension (ICH). However, the pre-test probability of ICH based on the distribution of its independent predictors has not yet been estimated in hypertensive subjects with mildly elevated blood pressure. OBJECTIVE: To ascertain the independent predictors of ICH in mildly hypertensive subjects. METHODS: In the setting of the HARVEST-PIUMA collaboration, we studied 1564 subjects with hypertension stage I. At entry, all subjects were untreated and all underwent ABP monitoring and echocardiography. Diabetes, hypertension grade > I, renal failure or previous cardiovascular morbid events were exclusion criteria. Clinic BP was 143/92 mmHg (SD 9/5) and 24 h ABP was 128/81 mmHg (SD 10/8). RESULTS: Prevalence of ICH (daytime ABP < 130 mmHg systolic and 80 mmHg diastolic) was 10.4%. In a multivariate logistic regression analysis, sex (P = 0.002), smoking (P = 0.038) and clinic diastolic BP (P = 0.0002) were the sole independent predictors of ICH according to the following equation: Y = 2.6438 + 0.5128 x sex (0 = men; 1 = women) + 0.4543 x current smoking (0 = yes; 1 = no) - 0.0531 x clinic diastolic BP (mmHg) and P (probability of ICH) = exp(Y)/[1 + (exp(Y)]. Left ventricular (LV) mass at echocardiography was a further independent predictor (P = 0.002) of ICH according to the following equation: Y= 3.4343 + 0.4603 x sex + 0.5989 x current smoking - 0.0482 x clinic diastolic BP - 0.0312 x LV mass [g/height (m)2.7]. LV mass was greater (P < 0.01) in the group with ambulatory hypertension [42.3 g/height (m)2.7] than in that with ICH [39.2 g/height (m)2.7] and not dissimilar between the ICH group and a control group of 370 healthy normotensive subjects [38.1 g/height (m)2.7]. CONCLUSIONS: In untreated subjects with stage I hypertension, ICH is most frequent among women, nonsmokers and subjects with low clinic BP and smaller LV mass. These findings allow identification of subjects with indication to ABP monitoring because of suspected ICH.