Use of Magnetic Resonance Imaging in the Evaluation ofAcute Cholecystitis in Emergency Setting.

Background Acute cholecystitis is one of the commonest surgical disease. The rapid diagnosis at its early stage is one of the crucial factor in patient care and management. Objective To evaluate the role of magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) in the diagnosis or exclusion of acute cholecystitis, coexisting choledocholithiasis, and acute pancreatitis in emergency setting. Method This study was conducted in the department of radiodiagnosis B and C teaching hospital, Birtamod, Nepal from July 2016 to November 2019. Patients, clinically diagnosed as acute cholecystitis or biliary condition with positive Murphy's sign with or without jaundice and deranged Liver Function Test, raised Leucocyte counts were evaluated by Magnetic Resonance imaging. The sensitivity, specificity, Positive Productive Value (PPV), Negative Productive Value (NPV) were calculated for the diagnosis of acute cholecystitis. Data was entered and analysed by using SPSS version 20. Result There were 40 patients included in our study. Among them 27 (67.5%) were females and 13 (32.5%) male. The age of the patients ranged from 16 years to 79 years, mean age 49.4 years. Majority of the patients were in the age group of 40-60 years (57.5%). The overall sensitivity, specificity, Positive Productive Value and Negative Productive Value of Magnetic Resonance imaging diagnosis of acute cholecystitis were 100%, 66.6%, 94.4% and 100% respectively. Acute cholecystitis associated with gall stone disease were common and found in 72.5% cases, with sensitivity 96.5%, specificity 27.7%, Positive Productive Value 77.7% and Negative Productive Value 75.0%. Conclusion Magnetic resonance imaging (MRI)/Magnetic resonance cholangiopancreatography (MRCP) is an excellent tool for the evaluation of biliary pathology and can be used for the preoperative evaluation of acute cholecystitis at the emergency setting.

Magnetic Resonance Imaging Evaluation of Musculoskeletal Diseases of Ankle and Foot.

Background Ankle and foot pain is a common clinical problem, that may be due to a variety of soft tissue and osseus abnormalities. Magnetic resonance imaging plays vital role for diagnosing internal derangement of the ankle joint, assessing soft tissue structures around the ankle such as tendons, ligaments, nerves and osseus structures. Method Retrospective magnetic resonance imaging evaluation of the ankle and foot was done in 100 patients using 0.3T and 1.5T magnetic resonance imaging. Clinical history included pain, swelling of the ankle and foot, trauma, twisting injury, palpable mass and difficulty in walking. Result Fifty two patients were male and 48 patients female aged 6 months to 70 years. Ligaments tear were the commonest and seen in 22% patients. Tenosynovitis found in 17%, Pigmented villonodular synovitis (PVNS) in 3%, Achilles tendon abnormality in 8%, stress fracture-9%, osteomyelitis-8%, soft tissue vascular malformation in 5%, soft tissue and bone tumor-4%, marrow edema-20%, osteoarthritis-10%, Osteochondral lesion of talus-8%, sinus tarsi syndrome-3%, posterior impingement-5%, plantar fasciitis-2%, Sever disease-2%, peroneus tendon split-2%. The commonest clinical presentation was pain and swelling of the ankle in 42 patients, twisting/inversion injury of the ankle in 23 patients followed by traumatic injury with difficulty in walking in 20 patients and palpable mass in 8 patients. Ligaments injury were mostly associated with inversion/twisting injury. Conclusion Magnetic resonance imaging is advantageous for assessing soft tissue structures around the ankle and foot, such as tendons, ligaments, nerves, masses and occult osseus lesions. It provides a quick, non-invasive tool for the diagnosis of related injuries and guide for the further treatment planning.

Pharmacological activities of cinnamaldehyde and eugenol: antioxidant, cytotoxic and anti-leishmanial studies.

The present study reports the antioxidant, cytotoxic and anti-leishmanial activities of cinnamaldehyde and eugenol. Both the compounds are naturally present in cinnamon and bay leaf. Eugenol is abundantly present in clove. The antioxidant potential was measured in terms of reducing power (FRAP assay), nitric oxide (NO) radical scavenging ability and anti-lipid peroxidative activities. MTT assay was used to evaluate the effect of test compounds on cell viability of prostate cancer cell line (PC-3) as well as for the assessment of in vitro growth inhibition of promastigotes as a measure of anti-leishmanial activity.  Eugenol exhibited considerable NO radical scavenging (63%) and reducing abilities (FRAP value 127×104 µM/mM) while cinnamaldehyde showed comparatively better protective efficacy against lipid peroxidation in rat brain and kidney homogenates (up to 40%). Cinnamaldehyde also displayed substantial cytotoxic activity (75%) against PC-3 cell line. Both the compounds exhibited moderate anti-leishmanial activity and IC50 values for eugenol and cinnamaldehyde were found to be 0.681 g/ml and 1.426g/ml, respectively. The study revealed that both the test compounds have noticeable antioxidant and cytotoxic activities.

Risk-based Management of Non-muscle Invasive Bladder Cancer: Experience from Tribhuvan University Teaching Hospital.

Background Most of the recent evidences suggest for risk-based management of non muscle invasive bladder cancer (NMIBC) to reduce the risk of recurrence and progression. Objective This study was conducted to assess the recurrence and progression of non muscle invasive bladder cancer in Nepalese patients using European Organization for Research and Treatment of Cancer (EORTC) risk tables and to assess the effectiveness of intravesical therapy to reduce the risk of recurrence. Method A prospective observational single centre study was conducted at Tribhuvan University Teaching Hospital from January 2010- December 2012. Forty six patients with non muscle invasive bladder cancer who underwent transurethral resection of bladder tumor and completed two years follow up were included. According to the European Organization for Research and Treatment of Cancer (EORTC) risk table, the patients were divided into low, intermediate and high risk groups. The patients received postoperative adjuvant therapy and surveillance as per the European Association of Urology guidelines. Result Among the 46 patients, the overall two year recurrence and progression rate was 8 (17%) and 1 (2%) respectively. Out of seven patients in low risk category, none of them developed recurrence or progression of disease. Out of 15 patients in intermediate risk category the one year and two year recurrence rate was 13% and 20% respectively. Out of 24 patients in high risk category the one and two year recurrence rate was 17% and 21% respectively. The risk reduction by use of intravesical Bacillus Calmette Guerin (BCG) for recurrence in high risk category was 58% and 60% in first and second year respectively. In our study, the overall and individual risk group, the one and two year recurrence rate was lower than that predicted by European Organization for Research and Treatment of Cancer risk table. Conclusion Risk-based management of non muscle invasive bladder cancer by using the European Organization for Research and Treatment of Cancer risk table is a useful method of management, though its prediction rates are lower in Nepalese population.

Cervical capillary haemangioma: a case report.

Capillary haemangioma is a common benign lesion occurring at multiple areas of body. They have unique radiological appearances and are confirmed by histological examinations. However capillary haemangioma of cervical region is a very rare condition. Such a case is presented here. It presented as an extramedullary intradural mass compressing the cord and corresponding root giving rise to myeloradiculopathic symptoms. Total enblock excision of the lesion gave a total cure.

Protective efficacy of Solanum xanthocarpum root extracts against free radical damage: phytochemical analysis and antioxidant effect.

Free radicals have been implicated in many diseases. They attack biological macromolecules in healthy human cells and cause protein and DNA damage along with lipid peroxidation. Present study reports the phytochemical analysis as well as free radical scavenging and antioxidant activities of Solanum xanthocarpum root extracts. Tannins, flavonoids, terpenoids, alkaloids, saponins and steroids were present in different extracts. Total flavonoid content in extracts was quantified and maximum contents were found in ethyl acetate fraction followed by chloroform and ethyl alcohol fractions, respectively. Dose dependent response was observed in metal ion chelating activity of extracts. Comparatively better chelating activity was found in polar extracts. Most of the extracts exhibited significant free radical scavenging activity in DPPH radical scavenging assay. Ethanolic and aqueous extracts accounted for about 40—50% lipid peroxidation inhibition (LPOI) in rat liver homogenate. Antioxidant activity did not show direct correlation with the amount of flavonoid contents in the extracts. However, direct correlation was observed between DPPH free radical scavenging activity and LPOI. Antioxidant activity of the extracts was compared with standard antioxidants. The differential activity observed in extracts could be attributed to the presence of other phytochemicals such as tannins and terpenoids in addition to flavonoids. The study demonstrated appreciable protective efficacy in S. xanthocarpum root extracts against free radical damage.

Phaeochromocytoma in Nepal--a single centre experience.

BACKGROUND: Phaeochromocytomas are rare tumors of chromaffin cells of neural crest that classically present with symptoms of catecholamine excess such as palpitations, headache and sweating. They are diagnosed by measuring plasma or urinary levels of catecholamines or their metabolites. Anatomic localization is done by computed tomographic scan or magnetic resonance imaging, or meta-iodobenzyl guanidine scan in certain cases. Adequate preoperative catecholamine blockade prevents perioperative hemodynamic instability. OBJECTIVES: To study the clinical spectrum and management of phaeochromocytomas in a tertiary care centre, Tribhuvan University Teaching Hospital, in Nepal. METHODS: Retrospective review of case records of histologically proven cases of phaeochromocytomas from 2008 -2011 was done, and data collected on clinical spectrum, diagnostic modalities, perioperative management and follow-up. RESULTS: Twelve cases of phaeochromocytomas were operated. The mean age was 36.41+/-14.07 years. There were 2 bilateral phaeochromocytomas and 1 extraadrenal paraganglioma. Apart from the common symptoms of catecholamine excess, patients had atypical presentations like psychiatric manifestations and blurred vision. A combination of urinary Vanillyl Mandelic Acid and computed tomographic scan was used for diagnosis, and open surgery was done in all cases. Pre-operative blood pressure control was achieved by prazocin or calcium channel blockers. Ten patients had intraoperative surge in blood pressure. There were no major morbidity or mortality. Three patients had high blood pressure postoperatively, but were effectively managed with antihypertensives. CONCLUSION: Phaeochromocytomas can have variable presentation. Good preoperative preparation and perioperative management can result in an excellent outcome.

Clinical, MRI and arthroscopic correlation in internal derangement of knee.

BACKGROUND: The traumatic or degenerative internal derangement of the knee requires certain investigations for the establishment of diagnosis, in addition to clinical history and a thorough physical examination. The use of arthrography and arthroscopy improves the accuracy of the diagnosis. MRI scanning of the knee joint has often been regarded as the noninvasive alternative to diagnostic arthroscopy. OBJECTIVE: The purpose of the study was to correlate clinical and low field MRI findings with arthroscopy in internal derangement of the knee. METHODS: Forty one patients with suspected internal derangement of the knee were subjected to MR examination followed by arthroscopy. Clinical criteria used were history, mode of injury, Mc Murray, Apley grinding, Thessaly test for meniscal injury. Drawer test was considered to be essential for clinical diagnosis of cruciate ligament injury. MRI of the knee was performed in low field open magnet (0.35T, Magnetom C, Seimens). Arthroscopy was done within two months of MR examination and was considered gold standard for the internal derangement of the knee. RESULTS: The sensitivity, specificity, diagnostic accuracy of clinical examination were 96.1%, 33.3% and 73.1% respectively for medial meniscal tear; 38.4%, 96.4% and 78.1% respectively for lateral meniscal tear. The sensitivity, specificity, diagnostic accuracy of MRI were 92.3%,100% and 95.1% for medial meniscal tear; 84.6%96.4% and 92.6% respectively for lateral meniscal tear. CONCLUSION: Clinical examination showed higher sensitivity for medial meniscal tear compared to MRI, however with low specificity and diagnostic accuracy. Low field MRI showed high sensitivity, specificity, diagnostic accuracy for meniscal and cruciate ligament injury, in addition to associated derangement like articular cartilage damage, synovial thickening.

Pattern of renal cell carcinoma - a single center experience in Nepal.

BACKGROUND: Renal tumor is the 13th most common malignancy in the world and more than 90% of renal tumors are renal cell carcinomas. As there is no data available on renal cell carcinoma in Nepal, hence this study was undertaken to analyze the patterns of renal cell carcinoma in patients with renal mass at a tertiary level hospital in Nepal. OBJECTIVES: To analyze the patterns of renal cell carcinoma in patients with renal mass at a tertiary level hospital in Nepal. METHODS: The case records of 50 consecutive patients with renal cell carcinoma presenting at the Tribhuvan University Teaching Hospital, Kathmandu from July 2006 to June 2011 were retrospectively evaluated for presenting symptoms, physical finding, investigation and histopathology report. RESULTS: Out of 50 patients, 64% were male and 36% were female. The age ranged between 11 to 78 years (mean ± SD: 55 ± 15 years). Fifty four percent of patients were smokers. Incidentally tumor was detected in 40% cases by ultrasonography and the typical triad was present in only 4%. The tumor was occupying upper pole in 40% of cases. The tumor size ranged from 3 to 15 cm (mean ± SD: 7.3 ± 2.9 cm). Histopathologically, 76% of the patient had organ confined renal cell carcinoma (T1- 2 N0 M0). Clear cell was the most common type seen in 86%. Fuhrman nuclear grade 2 was found in 50%. CONCLUSION: Many of the renal cell carcinoma are detected incidentally, at an early stage and are of clear cell subtype.

Plasma cell rich acute rejection: Risk factors, treatment and outcomes.

Plasma cell-rich rejection is a rare and poorly defined entity. Its treatment is not clearly defined and has universally poor prognosis. More data should be published from various transplant centers around the world to identify the treatment that has the best outcomes and to formulate treatment guidelines for these cases. It is a retrospective analysis of kidney biopsies form 2008 to 2018. Four hundred biopsied were screened and 55 were found to have features of rejection and among them, 13 had plasma cell-rich rejection. Data of treatment given and the graft survival outcomes in these cases were retrieved by medical records. One patient had complete recovery, three had graft loss and the remaining nine had permanent decline in glomerular filtration rate. Decrease in immunosuppression and presence of infection are risk factors for plasma cell-rich acute rejection (PCAR). It can be acute cell-mediated rejection (ACR)/antibody-mediated rejection (AMR)/ACR+AMR. Resistant rejection, ACR+AMR, C4d positivity, and severe interstitial inflammation are poor prognostic factors. Overzealous decrease in immunosuppression should not be done. Management of immunosuppression during infection is most critical for the development of PCAR. Bortezomib is emerging as a therapeutic modality for the treatment of PCAR.

Renal Transplantation: Experience at a Single Centre.

BACKGROUND: Renal transplantation program in the Armed Forces commenced in Feb 1991 and till date 245 patients have undergone renal transplantation at INHS Asvini. We describe our protocols for donor and recipient evaluation and immunosuppression. METHODS: 245 patients received renal transplants during this period, 243 (99.2%) being from live donors. Most of them were started on triple immunosuppression comprising of cyclosporine, azathioprine and prednisolone. Newer drugs like mycophenolate, tacrolimus and sirolimus were administered in a select population. RESULT: 69 (28.1%) of them had at least one episode of acute rejection, most of which were steroid responsive and 13 (18.8%) of them required either anti CD3 monoclonal or anti-thymocyte globulin (ATG). Complete recovery with normal renal function occurred in 54 (78.2%) cases and 15 (21.7%) recovered with residual dysfunction with maximum serum creatinine being 2.1mg/dl. There were three (1.2%) cases of accelerated rejection during the first week of transplantation and one had graft rupture. All three lost their grafts. There were eight (3.2%) cases of acute tubular necrosis, who recovered completely within 8-14 days. Immediate infections included wound sepsis, lower respiratory tract infection, disseminated candidiasis and disseminated aspergillosis. Late infections included pulmonary tuberculosis, disseminated tuberculosis, cytomegalovirus infection and recurrent urinary tract infection. 28 (11.4%) patients developed post transplant diabetes mellitus. At the end of one year and five years, graft and patient survival were 97.2%, 93%, 80.9% and 85.7% respectively. CONCLUSION: Our outcomes show that the transplantation is a viable mode of renal replacement therapy in patients of end stage kidney disease with a near normal rehabilitation.

Validation of an ultra-high-performance liquid chromatography-mass spectrometry method for the quantification of cysteinylated aldehydes and application to malt and beer samples.

This paper describes the method validation for the simultaneous determination of seven cysteinylated aldehydes, i.e. 2-substituted 1,3-thiazolidines-4-carboxylic acids, using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Authentic reference compounds were first synthesized for identification and quantification purposes. Moreover, nuclear magnetic resonance (1H NMR and 13C NMR) was applied for verification of their structure, while ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was applied for estimation of the purity. The method for quantification of cysteinylated aldehydes in model solutions has been validated according to the criteria and procedures described in international standards. The synthesized compounds were successfully identified via UHPLC-MS by comparing retention time and MS spectra with the commercial reference compounds. Method validation revealed good linearity (R2 > 0.995) over the range of 0.4-2.2 µg/L to approximately 1000 µg/L, depending on the analyte. The limits of quantification varied from 0.9 to 4.3 µg/L depending on the nature of the compound. Furthermore, evaluation of the method showed good accuracy and stability of the standard solutions. Reported chromatographic recoveries ranged from 112 to 120%. Consequently, the currently described method was applied on malt and beer samples. For the first time, quantification of cysteinylated aldehydes was obtained in malt. In contrast, in fresh beers unambiguous identification of these compounds was not achieved.

Intrathyroid metastasis presenting as a solitary thyroid nodule: an unusual case of clinically silent lung cancer.

Metastases in the thyroid gland are very rare. Carcinoma lung is one of the tumours, which may metastasize to the thyroid. We report a 60-year-old lady with intrathyroid metastasis presenting as a solitary thyroid nodule. Fine needle aspiration cytology from the nodule showed features of metastatic adenocarcinoma. Further detail evaluation revealed primary lung adenocarcinoma with secondaries to adrenals, retroperitoneal and bilateral axillary nodes. This report emphasizes this unusual clinical presentation of carcinoma lung with wide spread secondaries; and a solitary thyroid nodule can be a presenting complain of a metastatic disease.

Marker-Negative Pheochromocytoma Associated with Inferior Vena Cava Thrombosis.

Pheochromocytoma associated with inferior vena cava (IVC) thrombosis is very rare. A 27-year-old female presented with right flank pain and hypertensive urgency. Contrast-enhanced CT abdomen and gadolinium-contrast MRI abdomen revealed right adrenal mass suspicious of malignancy with invasion and compression to the right IVC wall along with IVC thrombus extending from the level of renal veins to the level of confluence with hepatic veins. Her routine laboratory investigations including 24-hour urine fractionated metanephrines, vanillylmandelic acid, and cortisol were normal. Right adrenalectomy with IVC thrombectomy was done. Perioperative period was uneventful. Histopathology of the mass turned out to be pheochromocytoma with thrombus revealing fibroadipose tissue with fibrin. Pheochromocytoma may present with IVC thrombus as well as normal serum and urinary markers. Thus, clinical suspicion is imperative in perioperative management of adrenal mass.

Intravesical foreign body: case report.

Foreign bodies of the urinary bladder may occur by self insertion or migration from the neighbouring organs. All the foreign bodies when left for long act as a nidus for calculus formation. The patient usually presents with dysuria, intermittent urinary tract infection or suprapubic pain. Here we report two cases of vesical foreign body which was removed by the cystoscopy.

Clinico-radiological profile of stroke in eastern Nepal: a computed tomographic study.

AIM: Stroke is a frequent cause of death and disability in elderly patients. This study was carried out to establish the pattern of various types of cerebrovascular accident (CVA) in eastern Nepal and to correlate the clinical data and radiological findings in cases of stroke. MATERIALS AND METHODS: All the patients clinically diagnosed as stroke and referred to the radiology department for Computed tomography (CT) of the brain over a period of 1 year were included. RESULTS: There were 150 patients with stroke (104 males and 46 females), aged 7 to 91 years in which infarction (58%) was more common than haemorrhage (42%) in both group of age (< or = 40 years and > 40 years). Smoking was the commonest risk factor noted in 40.66% cases followed by hypertension (40%). Excessive meat consumption (more than 4 times a week) was seen in 69.1% cases. In early Middle Cerebral Artery (MCA) territory infarction presenting within six hours of onset, positive CT findings were seen in 40% cases among which, obscuration of the lentiform nuclei was diagnostic. CONCLUSION: In this part of Nepal, infarction is more common than haemorrhage as the cause of stroke and in contrary to western population; hemorrhagic stroke constitutes a significantly higher proportion of stroke. Smoking is the commonest risk factor followed by hypertension and it is also seen in combination with alcohol in many cases. Excessive meat consumption could be an additional risk factor for stroke in this part of Nepal. In younger age group (< or = 40 years), haemorrhage is more common than infarction and alcohol consumption is the commonest risk factor.

Clinicopathological Pattern of Penile Cancer in a Tertiary Care Centre in Nepal.

INTRODUCTION: Carcinoma of penis is an uncommon entity. The higher incidence in developing country may be because of poor hygiene, less common practice of circumcision and unsafe sexual practice. Timely diagnosis and intervention gives the patient a chance of cure. Data on penile cancer is sparse from Nepal so treatment of penile cancer in our centre is presented here. METHODS: This was a retrospective cross-sectional study done at Urology unit of Department of Surgery of Tribhuvan University Teaching Hospital, Nepal from November, 2007 to December, 2013. Data was retrieved from case records and those with penile carcinoma were included. Patient demographics, lesion characteristics, mode of treatment with outcome measures were noted and analyzed. RESULTS: Total 17 patients underwent treatment for primary penile lesion. Mean age of the patients was 51.5 years. Penile growth was the most frequent presentation with five patients coming with more than one symptom. The most common site was over glans of penis (n=13) with the mean size of 3.55 cm. Partial penectomy was offered in 16 with one patient undergoing circumcision only. Inguinal lymph node dissection was done in four patients. Squamous cell carcinoma was the histological diagnosis in 15 patients. CONCLUSIONS: Penile carcinoma is primarily a disease of old. Growth over glans penis is the most common presentation and partial penectomy is feasible in most of the patients to allow oncological cure while preserving the organ for its native function.

Failure of insulin-like growth factor type I to suppress HIV type 1 in adult or umbilical cord mononuclear blood cells.

Insulin-like growth factor type I (IGF-I) has been used as a treatment for cachexia in adults with AIDS and has been reported to show inhibitory activity against HIV-1IIIB in cord blood mononuclear cells (CBMCs) in vitro at low-concentration (1%) fetal bovine serum (FCS). We evaluated the effect of IGF-I on MN, IIIB, and BaL strains, as well as on a patient isolate of HIV-1 in CBMCs and adult peripheral blood mononuclear cells (PBMCs). IGF-I failed to show any inhibitory effect on HIV replication in CBMCs or adult PBMCs under various culture conditions. In contrast to an earlier report of an antiviral effect, IGF-I augmented HIV-1 replication in PHA-stimulated PBMCs maintained in a low concentration of FCS.

Naturally occurring HIV-1 isolates with differences in replicative capacity are distinguished by in situ hybridization of infected cells.

Replication of human immunodeficiency virus type 1 (HIV-1) isolates in peripheral blood mononuclear cells (PBMC) has been studied by in situ hybridization using the riboprobe BH10-R3 from HTLV-IIIB. Two series of isolates were tested: (a) 20 isolates from individuals with varying severity of HIV-1 infection and (b) sequential isolates from 5 subjects showing signs of clinical progression over a 45 month observation period. The results show that HIV-1 isolates with distinct replicative capacity can be distinguished by the intensity of radioactive labeling over single infected cells after in situ hybridization. Sequential isolates from patients with clinically progressive HIV-1 infection show a gradual increase in replicative capacity over time. In PBMC cultures infected with such sequential isolates, intensity of radioactive label over single infected cells increases and is strongest with isolates obtained at the time of low CD4 counts in blood. The results suggest that the restriction of virus replication that operates in the early stages of HIV-1 infection is gradually lost with progression of the disease.

Deletion analysis of the essentiality of penicillin-binding proteins 1A, 2B and 2X of Streptococcus pneumoniae.

An internal fragment from each of the penicillin-binding protein (PBP) 1A, 2B and 2X genes of Streptococcus pneumoniae, which included the region encoding the active-site serine residue, was replaced by a fragment encoding spectinomycin resistance. The resulting constructs were tested for their ability to transform S. pneumoniae strain R6 to spectinomycin resistance. Spectinomycin-resistant transformants could not be obtained using either the inactivated PBP 2X or 2B genes, suggesting that deletion of either of these genes was a lethal event, but they were readily obtained using the inactivated PBP 1A gene. Analysis using the polymerase chain reaction confirmed that the latter transformants had replaced their chromosomal copy of the PBP 1A gene with the inactivated copy of the gene. Deletion of the PBP 1A gene was therefore tolerated under laboratory conditions and appeared to have little effect on growth or susceptibility to benzylpenicillin.